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MOD Exam 2 > Intro to Neoplasia > Flashcards

Intro to Neoplasia Flashcards

1
Q

General features of benign tumors

A
  • -oma
  • Adenoma
  • Papilloma
  • Cystadenofibroma
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2
Q

Malignant neoplasms of epithelial cell origin, derived from any of the 3 germ layers

A

Carcinoma

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3
Q

Malignant tumors arising in solid mesenchymal tissues

A

Sarcoma

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4
Q

Malignant tumors arising from blood-forming cells

A

Leukemia or lymphoma

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5
Q

Generic term for all malignant neoplasms

A

Cancer

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6
Q

Literally “new growth or form”
- “results from genetic alterations that are passed down to progeny of the tumor cells”
- These genetic changes allow excessive and unregulated
proliferation that becomes autonomous (independent of
physiologic growth stimuli.)
- Occurs in a spectrum from benign to malignant

A

Neoplasia

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7
Q

(swelling) first used as one of the characteristics of

acute inflammation. Now frequently used by physicians as a synonym for neoplasia

A

Tumor

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8
Q

Study of tumors (neoplasms); medical oncology, surgical

oncology, pediatric oncology …

A

Oncology

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9
Q

The entire population of a neoplasm arises from a single cell that has incurred genetic change… i.e., all neoplastic cells are clones of one original altered cell.

A

Clonal

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10
Q

Ectodermal Derivatives

A
  • Skin
  • Nervous System
  • Teeth
  • Eye
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11
Q

Mesodermal Derivatives

A
  • Bone/cartilage
  • Fat
  • Muscle
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12
Q

Endodermal Derivatives

A
  • Respiratory Tract
  • GI tract
  • Thyroid gland
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13
Q

Malignant

A

Can invade and destroy adjacent structures and spread to distant sites (metastasis) to cause death

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14
Q

Major Categories of Malignancy

A

• carcinomas
– squamous cell carcinoma
– adenocarcinoma
– secondary descriptors

• sarcomas
– primary descriptors
– secondary descriptors

• blood forming cells
– leukemias, lymphomas, etc

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15
Q

The most common general category of malignant tumor in US adults

A

Carcinoma

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16
Q

Types of Lung Cancer

A
  • ADENOCARCINOMA (38%)
  • Squamous cell carcinoma (20%) • Small cell carcinoma (14%)
  • Large cell carcinoma (3%)
  • Other (25%)
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17
Q

Difference between a mixed tumor and teratoma?

A
  • Teratoma = more common in women and has at least 2 germ cell lineages
  • Mixed Tumor= All come from the same germ cell lineage
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18
Q

What are the 2 basic tissue components of benign and malignant neoplasms?

A
  1. Parenchyma: Generally gives rise to the neoplastic cellular component, it is benign,
    malignant or “other”
  2. Stroma: the supportive cellular component (the
    tissue “skeleton” upon which (or within which) the parenchymal component resides)
    - Generally not neoplastic (in carcinomas)
    - Typically consists of:
    ~ Connective tissue- supporting framework
    ~ Blood vessels
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19
Q

A group of cells, frequently arranged around a

lumen. The cells are typically specialized to secrete a substance.

A

Gland

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20
Q

Parenchyma, in terms of malignant transformation, is generally associated with?

A

Carcinoma

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21
Q

Stroma, in terms of malignant transformation, IF occurs, is generally associated with?

A

Saracoma

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22
Q

Difference between the structure of normal and cancer cells?

A

Normal:

  • Large cytoplasm
  • Single nucleus
  • Single nucleolus
  • Fine chromatin

Cancer

  • Small cytoplasm
  • Multiple nuclei
  • Multiple and large nucleoli
  • Coarse chromatin
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23
Q

The replacement of one type of cell with another type

A

Metaplasia

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24
Q

Literally means “disordered growth”

A

Dysplasia

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25
Q

Degree to which a neoplasm resembles the tissue from which it arises or is derived.

A

Differentiation

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26
Q

Two major determinants of differentiation

A
  1. The neoplastic cells nuclei and cytoplasm

2. The architectural relationship of the neoplastic cells to other neoplastic cells and non-neoplastic stroma.

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27
Q

The less differentiated a malignant neoplasm, the more ? its biologic behavior

A

Agressive
- Benign neoplasms are “well differentiated “ and may be
difficult to distinguish from normal tissue; e.g. lipoma.

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28
Q

2 Well Differentiated Benign Tumors

A
  1. Leiomyoma : benign, well-differentiated tumor contains interlacing bundles of neoplastic smooth muscle cells virtually identical to normal smooth muscle cells
  2. Thyroid Adenoma: unremarkable (well-differentiated) colloid-filled thyroid follicles
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29
Q

Grades of Differentiation

A
  1. Well differentiated: closely resembles parent tissue
  2. Moderately differentiated: features of the original tissue type identifiable, but it’s not the dominant pattern, with additional atypia
  3. Poorly differentiated: a small minority of cellular constituents allow identification of the parent tissue; associated with cellular anaplasia
  4. Undifferentiated: Tissue of origin cannot be discerned by histopathologic appearance of the neoplasm. Almost always associated with anaplasia.
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30
Q

Differentiation in Squamous Cell Carcinoma

A
  • WELL differentiated tumor cells have prominent keratin production and intercellular bridges present.
  • MODERATELY differentiated carcinoma has a significantly more distorted architecture
  • POORLY differentiated tumor has little organization, and keratin present but it is frequently only detected with special techniques
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31
Q

Differences between Benign and Malignant Tumors

A

▪ Benign and malignant tumors can be distinguished from one another based on the degree of differentiation, rate of growth, local invasiveness, and distant spread.

▪ Benign tumors often resemble the tissue of origin and are well differentiated; malignant tumors are less well differentiated or completely undifferentiated (anaplastic).

▪ Benign tumors are more likely to retain functions of their cells of origin, whereas malignant tumors sometimes acquire unexpected functions due to derangements in differentiation.

▪ Benign tumors are slow growing and mitotic figures are rare and normal; malignant tumors generally grow faster and have numerous or abnormal mitotic figures.

▪ Benign tumors are circumscribed and may have a capsule; malignant tumors are poorly circumscribed and tend to invade surrounding normal tissues.

▪ Benign tumors remain localized at the site of origin, whereas malignant tumors have the capability to metastasize to distant sites.

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32
Q

The one unequivocal criterion of malignancy

A

Metastasis

second is invasiveness

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33
Q

Examples of Malignant Neoplasms that have inappropriate benign terminology

A
  • Mesothelioma (Benign name: Benign fibrous tumor) = Mesothelium
  • Seminoma = Testicular epithelium
  • Malignant melanoma (Benign name: Nevus) = Tumors of Melanocytes
  • Wilms Tumor = Renal anlage
  • Immature teratoma (Benign name: Mature teratoma, dermoid cyst) = Totipotential cells in gonads or in embryonic rests
  • Lymphoma
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34
Q

Local INVASION of Malignant Tumors

A
  • Metastasis is defined by the spread of a tumor to sites that are physically discontinuous with the primary tumor, and unequivocally marks a tumor as malignant - by definition, benign neoplasms do not metastasize .
  • The invasiveness of cancers permits them to penetrate blood vessels, lymphatics, and body cavities, providing the opportunity for spread. All malignant tumors can metastasize, but some do so very infrequently (ex. gliomas-
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35
Q

The most common tumors in men arise in the ?

A
  • Prostate
  • Lung
  • Colon/rectum
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36
Q

In women, the most frequent cancers are in ?

A
  • Breast
  • Lung
  • Colon/rectum
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37
Q

Cancers of the ? constitute more than 50% of cancer diagnoses and cancer deaths in the United States

A
  • lung
  • female breast
  • prostate
  • colon/rectum
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38
Q

In contrast, in the developing world the most common cancers involve the ? in men, and the ? in women.

A
  • men: lung, stomach and liver

- women: breast, cervix, and lung

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39
Q

Tumors arising in the context of chronic inflammation are mostly ?, but also include ? and several kinds of ?. Immunodeficiency states predispose to ? cancers.

A
  • carcinomas
  • mesothelioma
  • lymphoma
  • virus-induced
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40
Q

?, the most common general category of cancer in adults, are extraordinarily rare in children

A

Carcinomas

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41
Q

Most carcinomas occur in the ?. Cancer is the main cause of death among women aged ? and among men aged ?; the decline in deaths after age ? is due to the lower number of individuals who reach that age.

A
  • later years of life (>55 years)
  • 40 to 79
  • 60 to 79
  • 80
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42
Q

Acquired conditions that predispose to cancer can be divided into ?

A
  • chronic inflammations
  • precursor lesions
  • immunodeficiency states.
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43
Q

4 classes of regulatory genes – the principal targets of cancer-causing mutations, tend to be affected

A
  1. Growth-promoting proto-oncogenes
  2. Growth-inhibiting tumor suppressor genes
  3. Genes that regulate apoptosis
  4. DNA-repair genes
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44
Q

Conversion of one of the two alleles from a proto-oncogene to an oncogene is sufficient to promote ?. However, it requires loss of BOTH ? alleles to promote neoplasia, as one of the two gene (protein) products is sufficient to inhibit neoplasia

A
  • neoplasia

- tumor suppressor

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45
Q

Include DNA methylation, which tends to silence gene expression, and modifications of histones, the proteins that package DNA into chromatin, which depending on their nature may either enhance or dampen gene expression.

A

Epigenetic modifications

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46
Q

? and ? dictate which genes are expressed, which in turn determines the lineage commitment and differentiation state of both normal and neoplastic cells.

A
  • DNA methylation

- histone modifications

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47
Q

The study of changes in gene expression that occur without changes in DNA sequence
- These changes are reversible, but sometimes stable and heritable

A

Epigenetics

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48
Q

3 types of Epigenetic alterations

A
  1. Methylation of DNA
  2. Modification of histones
  3. RNA-mediated modifications
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49
Q

8 hallmarks of cancer

A
  1. Self-sufficiency in growth signals
  2. Insensitivity to growth-inhibitory signals
  3. Altered cellular metabolism
  4. Evasion of apoptosis
  5. Limitless replicative potential (immortality?)
  6. Sustained angiogenesis
  7. Ability to invade and metastasize
  8. Ability to evade host immune response
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50
Q

Molecular Hallmarks of Cancer

A
  • Avoiding immune destruction
  • Evading growth suppressors
  • Enabling replicative immortality
  • Tumor-promoting inflammation
  • Activating invasion and metastasis
  • Genomic instability (mutator phenotype)
  • Inducing angiogenesis
  • Resisting cell death
  • Deregulating cellular energetics
  • Sustaining proliferative signaling
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51
Q

Growth factor receptors

A
  • EGF receptor family

- ALK (receptor tyrosine kinases)

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52
Q

Proteins involved in signal transduction

A
  • RAS proteins
  • ABL (non-receptor tyrosine kinase)
  • BRAF
  • SHH/WNT
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53
Q

A set of chemical reactions in a cell that occurs when a molecule, such as a hormone, attaches to a receptor on the cell membrane. The pathway is actually a cascade of biochemical reactions inside the cell that eventually reach the target molecule or site of reaction

A

Signal Transduction Pathway

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54
Q

Nuclear regulatory proteins

A

MYC

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55
Q
  • ERBB1 encodes the ?, which is involved by point
    mutations in certain cancers.
  • Of greatest clinical importance are several different ERBB1
    point mutations that are found in a subset of ?. These mutations result in constitutive activation of the ?
A
  • epidermal growth factor receptor (EGFR)
  • lung adenocarcinomas
  • EGFR tyrosine kinase
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56
Q
  • ERBB2 encodes a different member of the receptor tyrosine kinase family, ?.
  • Rather than being activated by point mutations, the ERBB2 gene is amplified in certain ?, leading to overexpression of the HER2 receptor and constitutive tyrosine kinase activity.
A
  • HER2

- breast carcinomas

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57
Q

GENE REARRANGEMENTS activate other receptor tyrosine kinases, such the tyrosine kinase
?

A

ALK

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58
Q

Included in the ALK group of receptor tyrosine kinases are the ? neurotrophin receptor genes (A, B, C) which have a crucial role in the growth, survival and differentiation of neural cells.

  • Clinically, they are notably useful as prognostic indicators in children with ? (and an important known association for MYC, as well)
A
  • TRK

- neuroblastoma

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59
Q

Point mutations of ? family genes constitute the most common type of abnormality involving proto-oncogenes in human tumors.

A

RAS

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60
Q

3 RAS genes in humans

A

HRAS, KRAS, NRAS

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61
Q

The RAS genes, of which there are three in humans were discovered initially in ?

A

transforming retroviruses

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62
Q
  • Mutations in ?, a member of the RAF family, have been detected in close to 100% of hairy cell leukemias, more than 60% of melanomas, 80% of benign nevi, and a smaller percentage of a wide variety of other neoplasms, including colon carcinomas and dendritic cell tumors.
  • a serine/threonine protein kinase that sits at the top of a cascade of other serine/threonine kinases of the MAPK family. Like activating RAS mutations, activating mutations in ? stimulate each of these downstream kinases and ultimately activate transcription factors.
A

BRAF

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63
Q

?, the failure (of the embryonic prosencephalon to divide) to form cerebral hemispheres, is commonly linked to mutations in genes involved in the ? pathway.

A
  • Holoprosencephaly

- hedgehog

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64
Q

?, the most common form of human cancer, has the closest association with hedgehog signaling

A

Basal cell carcinoma

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65
Q

Abnormal activation of the pathway probably leads to development of disease through transformation of ? stem cells into ? stem cells that give rise to the tumor.

A
  • adult

- cancer

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66
Q

The ? signaling pathways are a group of signal transduction pathways distinct from but related to HH (hedgehog) pathways.

A

Wnt

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67
Q
  • The most common malignant brain tumor of childhood, is an aggressive, diverse and heterogeneous cancer.
  • Although it is most frequent in children between the ages 0 and 9, it can occur at any age.
A

Medulloblastoma

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68
Q

It is believed that ? induces neoplasia by aberrant effects on adult stem cells.

A

SHH

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69
Q
  • ? (a proto-oncogene and the prototypical nuclear regulatory protein) is most commonly involved in human tumors.
  • A major transcriptional regulator of cell growth
  • expressed in virtually all eukaryotic cells and belongs to the immediate early response genes, which are rapidly and transiently induced by RAS/MAPK signaling following growth factor stimulation of quiescent cells.
A

MYC

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70
Q

Any organism whose cells contain a nucleus and other organelles enclosed within membranes.

A

Eukaryote

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71
Q

Single-celled organism that lacks a membrane- bound nucleus, mitochondria, or any other membrane- bound organelle.

A

Prokaryote

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72
Q

A small infectious agent that replicates only inside the living cells of other organisms.

A

Virus

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73
Q

MYC:
- Activates the expression of ? genes that are involved in cell growth

  • In certain circumstances, MYC upregulates expression of ?
  • Can act to reprogram somatic cells into ? stem cells
  • MYC paralogs= ?
  • In ?, MYC is deregulated by a variety of mechanisms (including mutation of MYC itself, and amplification in other neoplastic settings)
  • associations with ? (and other B and T cell tumors), neuroblastoma, and many common carcinomas
A
  • many
  • telomerase
  • pluripotent
  • NMYC and LMYC
  • cancer
  • Burkitt lymphoma **
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74
Q

A gene that is related to another gene by descent from a single ancestral gene that was duplicated and that may have a different DNA sequence and biological function.

A

Paralog

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75
Q

Many tumor suppressors, such as ? and ?, are part of a regulatory network that recognizes genotoxic stress from any source and responds by shutting down proliferation.

A
  • Rb and p53
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76
Q

Tumor Suppressor Genes:

Inhibitors of mitogenic signaling pathways

A
  • APC (AD inheritance)
  • NF1 (AD)
  • NF2 (AD)
  • PTCH
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77
Q

Tumor Suppressor Genes:

Inhibitors of cell cycle progression

A

RB (AD)

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78
Q

Tumor Suppressor Genes:

Inhibitors of pro-growth programs of metabolism and angiogenesis

A

VHL (AD)

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79
Q

Tumor Suppressor Genes:

Inhibitors of Invasion and metastasis

A

CDH1 (E-cadherin)

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80
Q

Tumor Suppressor Genes:

Enablers of genomic stability

A

TP53 (cell cycle checkpoint component) (AD)

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81
Q

Tumor Suppressor Genes:

DNA repair factors

A
  • BRCA1, BRCA2

* MSH (AR)

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82
Q

Tumor Suppressor Genes:

Unknown Mechanisms

A

WT1

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83
Q
  • “two hit” hypothesis of oncogenesis in retinoblastoma/the ? gene
  • “The governor of proliferation”
A

RB

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84
Q

“the guardian of the genome” – the most frequently mutated

gene in human cancers

A

TP53

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85
Q

“gatekeeper of colonic neoplasia”

A

APC

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86
Q

A gene related to certain CNS tumors, renal cysts, neuroendocrine
tumors and renal cell carcinoma

A

VHL

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87
Q

Fusion gene

A

BCR-ABL

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88
Q

2 cell cycle checkpoint components

A

Rb and p53

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89
Q

Tumor suppressor “pocket” protein that binds E2F transcription factors in its hypophosphorylated state, preventing G1/S transition; also interacts with several transcription factors that regulate differentiation

A

Rb

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90
Q
  • Tumor suppressor altered in the majority of cancers; causes cell cycle arrest and apoptosis.
  • Acts mainly through p21 to cause cell cycle arrest. Causes apoptosis by inducing the transcription of pro-apoptotic genes such as BAX. Levels of ? are negatively regulated by MDM2 through a feedback loop.
  • required for the G1/S checkpoint and is a main component of the G2/M checkpoint.
A

p53

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91
Q
  • In FAMILIAL cases, children inherit one defective copy of the RB gene in the ? (the first hit), and the other copy is normal. Retinoblastoma develops when the normal RB allele is mutated in retinoblasts as a result of a spontaneous ? mutation (as the second hit).
  • In sporadic cases both normal RB alleles must undergo ? mutation in the same retinoblast (two hits).
A
  • germline
  • somatic
  • somatic
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92
Q

Loss of normal cell cycle control is central to malignant transformation and that at
least one of four key regulators of the cell cycle (?) is
dysregulated in the vast majority of human cancers.

A
  • p16/INK4a
  • cyclin D
  • CDK4
  • RB
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93
Q
  • a tumor suppressor gene that regulates cell cycle progression, DNA repair, cellular senescence and apoptosis, is the most frequently mutated gene in human cancers.
  • Loss of function mutations located on chromosome ?
A
  • TP53

- 17p13.1

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94
Q

Tumors with ? TP53 alleles are more likely to be killed by such therapy (irradiation and conventional chemotherapy) than tumors with ? TP53 alleles

A
  • wild type

- mutated

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95
Q

Inheritance of a mutated copy of TP53 predisposes individuals to malignant tumors because only one additional “hit” in the lone normal allele is needed to abrogate TP53 function.

  • Such individuals, said to have the ? syndrome, have a 25-fold greater chance of developing a malignant tumor by age 50 than the general population.
A

Li-Fraumeni

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96
Q

pRB is associated with which high risk HPV protein?

A

E7

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97
Q

p53 is associated with which high risk HPV protein?

A

E6

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98
Q

Loss of function mutation on this gene is associated with Wilms tumor (pediatric kidney cancer)

A

WT1

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99
Q

The newest and most rapidly developing frontier in cancer treatment

A

Immunotherapy

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100
Q

a protein that in humans is encoded by the CD274 gene

A

PD-L1

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101
Q

A checkpoint protein on T cells. It normally acts as a type of “off switch” that prevents T cells from attacking other cells in the body.

A

PD-1

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102
Q

Monoclonal antibodies that target either ? or ? can block this binding and boost the immune response to
cancer cells.

A
  • PD-1 or PD-L1
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103
Q
  • A protein receptor that functions as an immune checkpoint to downregulate immune responses.
  • Constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers.
  • It acts as an “off” switch when bound to CD80 or CD86 on the surface of antigen-presenting cells].
A

CTLA4

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104
Q
  • A monoclonal antibody that attaches to CTLA-4, blocking its expression.
  • It has been utilized to treat melanoma of the skin and certain other cancers.
A

Ipilimumab (Yervoy)

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105
Q
  • A major (perhaps predominant) enzyme that degrades the second messenger - cAMP - in many immune cells, including eosinophils, neutrophils, macrophages, T cells, and monocytes.
  • Proinflammatory mediators released by those cells lead to activation of and tissue infiltration by other immune cells, as well as activation and hyperproliferation of keratinocytes; this process could play a role in the development of ? lesions
A
  • Phosphodiesterase 4 (PDE4)

- psoriatic

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106
Q
  • Evidence suggests that ? causes a downregulatory signal in immune cells, thus suppressing the production of proinflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-17, and interferon (IFN)-γ.
  • It is also believed that cAMP promotes the production of anti-inflammatory mediators such as IL-10.
A

cAMP

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107
Q

The most common cancer in the United States.

-? patients had a 12 percent increased risk of developing it

A

non-melanoma skin cancer

  • psoriasis
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108
Q

Additional, intrinsic features characteristic of malignancy due to identified molecular features

A
  • Genomic instability
  • Cancer-enabling inflammation
  • Dysregulation of cancer-associated genes
  • Epigenetic changes
  • Non-coding RNAs and cancer
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109
Q

Chronic myelogenous leukemia (CML)

  • Translocation = ?
  • Gene = ?
A
  • Translocation = (9;22)(q34;q11)
  • Gene:
    ~ ABL 9q34
    ~ BCR 22q11
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110
Q

Acute myeloid leukemia (AML)

- Translocation = ?

A

Translocation:

  • (8;21)(q22;q22)
  • (15;17)(q22;q21)
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111
Q

Burkitt lymphoma

- Translocation = ?

A

(8;14)(q24;q32)

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112
Q

Mantle cell lymphoma

- Translocation = ?

A

(11;14)(q13;q32)

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113
Q

Follicular lymphoma

- Translocation = ?

A

(14;18)(q32;q21)

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114
Q

? changes have important roles in many aspects of the malignant phenotype, including the expression of cancer genes, the control of differentiation and self-renewal, and even drug sensitivity and drug resistance.

A

Epigenetic

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115
Q

2 types of non-coding RNAs

A
  1. Micro-RNA

2. Long noncoding RNA

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116
Q
  • Do not encode proteins; instead, they function primarily to modulate the translation of target mRNAs into their corresponding proteins.
  • Posttranscriptional silencing of gene expression by ? is a fundamental and well-conserved mechanism of gene regulation present in all eukaryotes (plants and animals).
A

Micro-RNA (miRNA)

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117
Q

bind to regions of chromatin, restricting RNA polymerase access to coding genes within the region.

A

Long noncoding RNA

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118
Q

Regulatory genes:

DNMT3A

  • Function = ?
  • Tumor = ?
A
  • DNA methylation

- Acute myeloid leukemia (20%)

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119
Q

MLL1

  • Function = ?
  • Tumor = ?
A
  • Histone methylation

- Acute leukemia in infants (90%)

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120
Q

MLL2

  • Function = ?
  • Tumor = ?
A
  • Histone methylation

- Follicular lymphoma (90%)

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121
Q

CREBBP/EP300

  • Function = ?
  • Tumor = ?
A
  • Histone acetylation

- Diffuse large B cell lymphoma (40%)

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122
Q

ARID1A

  • Function = ?
  • Tumor = ?
A
  • Nucleosome positioning/chromatin remodeling

- Ovarian clear cell carcinoma (60%), endometrial carcinoma (30%-40%)

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123
Q

SNF5

  • Function = ?
  • Tumor = ?
A
  • Malignant rhabdoid tumor (100%)
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124
Q

PBRM1

  • Function = ?
  • Tumor = ?
A
  • Renal carcinoma (30%)
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125
Q

Radiation carcinogenesis:

? is clearly implicated in the causation of skin cancers

A

“UV light

126
Q
  • ? are associated with total cumulative exposure to UV radiation, whereas ? are associated with intense
    intermittent exposure—as occurs with sunbathing”.
A
  • Nonmelanoma skin cancers

- melanomas

127
Q

Most frequent radiation induced cancer is?

- Cancer of the ? follows closely but only in the young

A
  • Myeloid leukemia

- thyroid

128
Q

Oncogenic RNA viruses

A

HTLV-1

129
Q

Oncogenic DNA viruses

A
  • HPV
  • EBV (and Burkitt lymphoma)
  • HBV (and HCV although an RNA virus)
  • Merkel cell polyomavirus (MCV)
  • HHV-8
130
Q 
Tumor Markers (Hormones) vs Tumor Types: 
- Human chorionic gonadotropin
  • Calcitonin
  • Catecholamine and metabolites
  • Ectopic hormones
A

Tumor Types:
- Trophoblastic tumors, nonseminomatous testicular tumors

  • Medullary carcinoma of thyroid
  • Pheochromocytoma and related tumors
  • See table 7-11
131
Q

Tumor Markers (Onofetal Antigens) vs Tumor Types:

  • alpha- Fetoprotein
  • Carcinoembryonic antigen
A
  • Liver cell cancer, nonseminomatous germ cell tumors of testis
  • Carcinomas of the colon, pancreas, lung, stomach, and heart
132
Q 
Tumor Markers (Isoenzymes) vs Tumor Types: 
- Prostatic acid phosphatase
  • Neuron- specific enolase
  • Specific proteins
A

Tumor Types:

  • Prostate cancer
  • Small-cell cancer of lung, neuroblastoma
  • Multiple myeloma and other gammopathies
133
Q 
Tumor Markers (Immunoglobulins) vs Tumor Types: 
- Prostate-specific antigen and prostate- specific membrane antigen
A

Prostate cancer

134
Q 
Tumor Markers (Mucins and other glycoproteins) 
- CA-125
  • CA-19-9
  • CA-15-3
A
  • Ovarian cancer
  • Colon cancer, pancreatic cancer
  • Breast cancer
135
Q 
Tumor Markers (Cell-Free DNA Markers) 
- TP53, APC, RAS mutants in stool and serum
  • TP53, RAS mutants in stool and serum
  • TP53, RAS mutants in sputum and serum
  • TP53 mutants in urine
A
  • Colon cancer
  • Pancreatic cancer
  • Lung cancer
  • Bladder cancer
136
Q

As with PSA, CEA and AFP assays lack both ? and ? required for the early detection of cancers, but they are useful for detection of RECURRENCES after excision.

A
  • specificity

- sensitivity

137
Q

What are the markers for:

  • Testicular cancer = ?
  • Ovarian tumors = ?
  • Multiple myeloma and other secretory plasma cell tumors = ?
A
  • human chorionic gonadotropin (HCG)
  • CA-125
  • Immunoglobulin or light chains
138
Q

In 2008, it was estimated that there were about ? new cancer cases worldwide, leading to ? deaths (21,000 deaths per day).

Due to increasing population size and age, by 2030 it is projected that the number of cancer cases and cancer-related deaths worldwide will increase to ? and ?, respectively.

A
  • 12.7 million
  • 7.6 million
  • 21.4 million
  • 13.2 million
139
Q

Highest cancer INCIDENCE in 2014 in men? In women?

A
  • Men = Prostate

- Women = Breast

140
Q

Highest cancer DEATHS in 2014 in men? In women?

A

Both LUNG

141
Q

Prostate cancer has a very high incidence in which countries?

A

North America and South America and Australia and Western European countries

142
Q

Breast cancer has a very high incidence in which countries?

A

Canada, US, Australia, Argentina, Sweden and Norway and some Western European countries

143
Q

A tumor is said to be ? when its gross and microscopic appearances are considered relatively innocent, implying that it will remain localized, will not spread to other sites, and is amenable to local surgical removal

A

Benign

144
Q

? tumors can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death

A

Malignant

145
Q
  • When a neoplasm, benign or malignant, produces a macroscopically visible projection above a mucosal surface and projects, for example, into the gastric or colonic lumen, it is called a ?
  • If the polyp has glandular tissue, it is called a ?
A
  • Polyp

- Adenomatous polyp

146
Q

Mixed tumor of Salivary Gland vs Adenoma of Colon:

  • Adenoma of the colon would have a ? that resembles the glands of the colon, and is not a mixed tumor
  • In most benign and malignant neoplasms, all the parenchymal cells closely resemble one another. Infrequently, however, divergent differentiation of a single neoplastic clone creates a mixed tumor, like the mixed tumor of the salivary gland. These tumors contain epithelial components scattered around a myxoid stroma that may contain islands of cartilage or bone. All of these elements arise from a ? clone capable of producing both epithelial and myoepithelial cells; thus, the preferred designation of this neoplasm is ?
A
  • parenchyma
  • single
  • pleomorphic adenoma.
147
Q

Cystic Teratoma of ovary vs Mixed Tumor of Salivary Gland:

The great majority of neoplasms, even mixed tumors, are composed of cells from a ? germ layer. BUT an exception is a tumor called a teratoma, which contains recognizable mature or immature cells or tissues belonging to ? germ cell layer.

A
  • single
  • more than one

Extra Info:
- Teratoma originates from totipotent germ cells that are normally present in the ovary and testis and sometimes also found in abnormal midline embryonic rests

  • Ovarian cystic teratoma (dermoid cyst), differentiates principally along ectodermal lines to create a cystic tumor lined by skin replete with hair, sebaceous glands, and tooth structures
  • ** Whereas the mixed tumor of the salivary gland arises from a single clone capable of producing multiple tissues, cystic teratomas of the ovaries arise from cells of two or three germ layers
148
Q

Why are benign tumors generally considered well differentiated?

A
  • The better the differentiation of the transformed cell, the more completely it retains the functional capabilities of its normal counterpart.
  • Thus benign neoplasms and well-differentiated carcinomas of endocrine glands frequently secrete hormones characteristic of their origin. Increased levels of these hormones in the blood are used clinically to detect and follow such tumors.
149
Q

Anaplasia (lack of differentiation) is associated with what morphological changes?

A
  • Pleomorphism
  • Abnormal nuclear morphology
  • Mitoses
  • Loss of polarity
  • Other changes
150
Q

Morphological change for Anaplasia:

What is Pleomorphism?

A
  • Variation in size and shape
  • Thus cells within the same tumor are not uniform, but range from small cells with an undifferentiated appearance, to TUMOR GIANT CELLS many times larger than their neighbors
151
Q

Morphological change for Anaplasia:

Abnormal nuclear morphology

A
  • Nuclei are disproportionally large for the cell, with a nuclear-to-cytoplasm ratio 1:1 instead of the normal 1:4 or 1:6
  • Nuclear shape is variable and often irregular
  • The chromatin is coarsely clumped and distributed along the nuclear membrane, or more darkly stained than normal (hyper chromatic)
  • Abnormally large nuclei
152
Q

Morphological change for Anaplasia:

Mitoses

A
  • Many cells are in mitosis, reflecting the high proliferative activity of the parenchymal cells (but not necessarily indicative of malignancy)
  • More important, are ATYPICAL, BIZARRE MITOTIC FIGURES, sometimes with tricolor, quadripolar, or multipolar spindles
153
Q

Morphological change for Anaplasia:

Loss of Polarity

A
  • The orientation of anaplastic cells is markedly disturbed

- Sheets or large masses of tumor cells grow in an anarchic, disorganized fashion

154
Q

Morphological change for Anaplasia:

Other Changes

A

Growing tumor cells require a blood supply, but often the vascular stroma is insufficient, and as a result in many rapidly growing malignant tumors develop large central areas of ischemic necrosis

155
Q
  • Defined as the replacement of one type of cell with another type
  • Nearly always found in association with tissue damage, repair, and regeneration
A

Metaplasia

156
Q
  • Literally means “disordered growth”
  • Encountered principally in epithelia and is characterized by a constellation of changes that include a loss in the uniformity of the individual cells as well as a loss in their architectural orientation
A

Dysplasia

157
Q

Describe the potential evolution of dysplasia in squamous epithelium

A
  • In dysplastic squamous epithelium the normal progressive maturation of tall cells in the basal layer to flattened squames on the surface may fail in part or entirely, leading to replacement of the epithelium by basal-appearing cells with hyper chromatic nuclei
  • Also, mitotic figures are more abundant than in the normal tissue and rather than being confined to the basal layer may instead be seen at all levels, including surface cells
158
Q

What distinguishes carcinoma in situ (CIS) from carcinoma?

A
  • When dysplastic changes are marked and involve the fulll thickness of the epithelium, but the lesion does not penetrate the basement membrane, it is considered a pre-invasive neoplasm and is referred to as CARCINOMA IN SITU
  • Once the tumor cells breach the basement membrane, the tumor is said to be INVASIVE
159
Q

Histopathological features used to assess rate of growth of a neoplasm

A
  • The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue, whereas nearly all benign tumors grow as cohesive expansile masses that remain localized to their site of origin and lack the capacity to infiltrate, invade, or metastasize to distant sites
160
Q

Local Expansion of Benign Tumors vs Localized Invasion by Malignant Tumors

A
  • Because benign tumors grown and expand slowly, they usually develop a rim of compressed fibrous tissue called a CAPSULE that separates them from the host tissue
  • This capsule consists largely of extracellular matrix deposited by stromal cells such as fibroblasts, which are activated by hypoxic damage resulting from the pressure of the expanding tumor
  • In contrast, malignant tumors are poorly demarcated from the surrounding normal tissue and a well-defined cleavage plane is LACKING
  • BUT slowly expanding malignant tumors may develop an apparently enclosing fibrous capsule and may push along a broad front into adjacent normal structures
  • Histo exam of such “PSEUDOENCAPSULATED” masses almost always show rows of cells penetrating the margin and infiltrating the adjacent structures, a CRABLIKE pattern of growth that constitutes the popular image of cancer
161
Q

Dissemination of cancers may occur through one of 3 pathways?

A
  1. Direct seeding of body cavities or surfaces
  2. Lymphatic spread
  3. Hematogenous spread
162
Q

Most common locations for metastasis?

A
  • Liver
  • Lungs
  • Bone
  • Brain
163
Q

Dissemination Path:

  • Occurs whenever a malignant neoplasm penetrates into a natural “open field” lacking physical barriers
  • Most often involved in the PERITONEAL cavity (but can be any cavity)
  • Characteristic of carcinomas arising in the ovaries, which not infrequently, spread to peritoneal surfaces, which become coated with a heavy cancerous glaze
A

Direct seeding of body cavities and surfaces

164
Q

Dissemination Path:

Transport through ? is the MOST COMMON pathway for the initial dissemination of carcinomas

  • ? may also use this route
  • Tumors do not contain functional lymphatics, but lymphatic vessels located at the tumor margins are apparently sufficient for this spread of tumors
A

LYMPHATIC SPREAD

  • lymphatics
  • Sarcomas
165
Q

Dissemination Path:

  • Typical of sarcomas but also seen with carcinomas
  • Arteries with their thicker walls, are less readily penetrated than are veins. Arterial spread may occur when tumor cells pass through the pulmonary capillary beds or pulmonary arteriovenous shunts or when pulmonary metastases themselves give rise to additional tumor emboli.
A

Hematogenous Spread

166
Q

Describe Lymphatic Spread:

  • The pattern of lymph node involvement follows the natural routes of lymphatic drainage
  • Because carcinomas of the breast usually arise in the upper outer quadrants, they generally disseminate first to the ?
  • Cancers of the inner quadrants drain to the nodes along the internal mammary arteries
  • Thereafter, the ? and ? nodes may become involved
  • Carcinomas of the lung arising in the major respiratory passages metastasize first to the perihilar ? and ? nodes
  • ? lymph nodes, however, may be bypassed (skip metastasis) because of venous-lymphatic anastomoses or because inflammation or radiation has obliterated lymphatic channels
A
  • Axillary lymph nodes
  • infraclavicular and supraclavicular
  • tracheobronchial and mediastinal
  • local
167
Q

The first node in a regional basin that receives lymph flow from the primary tumor

A

Sentinel node

168
Q

What is the Role of Sentinel Node in Staging Cancer?

A
  • Sentinel node mapping can be done by injection of radiolabeled tracers or colored dyes and exam of frozen sections of the sentinel lymph node performed during surgery can guide the surgeon to the appropriate therapy. Sentinel node exam has also been used for detecting the spread of melanomas, colon cancers, and other tumors
  • Drainage of tumor cell debris or tumor antigens, or both, also induces reactive changes within nodes. Thus enlargement of nodes may be caused by the spread and growth of cancer cells or reactive hyperplasia
  • ** Therefore, nodal enlargement in proximity to a cancer, while it must arouse suspicion, does not necessarily equate with dissemination of the primary lesion
169
Q

Hematogenous Spread

  • With VENOUS invasion, the blood borne cells follow the venous flow draining the site of the neoplasm and the tumor cells often rest in the first capillary bed they encounter. ? and ? are the most frequently involved in this because all portal area drainage flows to the ? and all canal blood flows to the ?.
  • Cancers arising in close proximity to the VERTEBRAL COLUMN often embolize through the paravertebral plexus, and this path is involved in the frequent vertebral metastases of carcinomas of the ? and ?
  • ? often invades the branches of the renal vein and then the renal vein itself, from where it may grow up the inferior vena cava, sometimes reaching the right side of the heart
  • ? often penetrate portal and hepatic radicles to grow within them into the main venous channels. Such intravenous growth may NOT be accompanied by widespread dissemination
A
  • Liver and lungs
  • liver
  • lungs
  • thyroid and prostate
  • Renal cell carcinoma
  • Hepatocellular carcinoma
170
Q

In epidemiology, is a measure of the probability of occurrence of a given medical condition in a population within a specified period of time. Sometimes loosely expressed simply as THE NUMBER OF NEW CASES DURING SOME TIME PERIOD

A

Incidence

171
Q

In epidemiology, is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is USUALLY EXPRESSED AS A FRACTION, AS A PERCENTAGE, OR AS THE NUMBER OF CASES PER 10,000 OR 100,000 PEOPLE.

A

Prevalence

172
Q

Or death rate, is a measure of the NUMBER OF DEATHS (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time.

A

Mortality

173
Q

Occupational Cancers:
Arsenic:

  • Cancer = ?
  • Typical use = ?
A
  • Cancer = Lung carcinoma, skin carcinoma
  • Typical use
  • By-product of metal smelting
  • Component of alloys
  • Electrical and semiconductor devices
  • Medications and herbicides
  • Fungicides
  • Animal dips
174
Q

Occupational Cancers:
Asbestos:

  • Cancer = ?
  • Typical use = ?
A

• Cancer

  • Lung
  • Esophageal
  • Gastric
  • Colon carcinoma
  • Mesothelioma

• Typical use

  • Used to be used in many applications because of fire, heat, and friction resistance
  • Still fund in existing construction and fire-resistant textiles
  • Friction materials (i.e., brake linings)
  • Underlayment and roofing papers
  • Floor tiles
175
Q

Occupational Cancers:
Benzene

  • Cancer = ?
  • Typical use = ?
A
  • Cancer = Acute Myeloid Leukemia
  • Typical use
  • Light oil
  • Exist in printing, lithography, paint, rubber, dry cleaning, adhesives and coating, and detergents
  • Formerly used as a solvent and fumigant
176
Q

Occupational Cancers:
Beryllium and Beryllium Compounds

  • Cancer = ?
  • Typical use = ?
A
  • Cancer = Lung carcinoma
  • Typical use
  • Missile fuel and SPACE vehicles
  • Hardener for lightweight metal alloys, particularly in aerospace applications and nuclear receptors
177
Q

Occupational Cancers:
Cadmium and cadmium compounds

  • Cancer = ?
  • Typical use = ?
A
  • Cancer = Prostate carcinoma
  • Typical use
  • Uses include YELLOW pigments and phosphors
  • Found in solders
  • Batteries and as alloy and in metal platings and coatings
178
Q

Occupational Cancers:
Chromium compounds

  • Cancer = ?
  • Typical use = ?
A

• Cancer = Lung carcinoma

• Typical use
- Component of metal alloys, paints, pigments, and preservatives

179
Q

Occupational Cancers:
Nickel compounds

  • Cancer = ?
  • Typical use = ?
A
  • Cancer = Lung and oropharyngeal carcinoma
  • Typical use
  • Nickel plating
  • Ferrous alloys, batteries, ceramics
  • By-product of stainless steel arc welding
180
Q

Occupational Cancers:
Radon and its decay products

  • Cancer = ?
  • Typical use = ?
A
  • Cancer = Lung carcinoma
  • Typical use
  • From decay of minerals containing uranium
  • Potentially serious hazard in quarries and underground mines
181
Q

Occupational Cancers:
Vinyl Chloride

  • Cancer = ?
  • Typical use = ?
A 
• Cancer = Hepatic angiosarcoma 
• Typical use 
- REFRIGERANT 
- Monomer for vinyl polymers 
- Adhesive for plastics 
- Formerly inert aerosol propellant in pressurized containers
182
Q

Chronic Inflammatory States and Cancer:
Asbestosis, silicosis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Mesothelioma, lung carcinoma

* Agent = Asbestos fibers, silica particles

183
Q

Chronic Inflammatory States and Cancer:
Inflammatory Bowel Disease

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Colorectal carcinoma

* Agent = —

184
Q

Chronic Inflammatory States and Cancer:
Lichen sclerosis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Vulvar squamous cell carcinoma

* Agent = —

185
Q

Chronic Inflammatory States and Cancer:
Pancreatitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Pancreatic carcinoma

* Agent = Alcoholism, germline mutations (e.g., in the trypsinogen gene)

186
Q

Chronic Inflammatory States and Cancer:
Chronic cholecystitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Gallbladder cancer

* Agent = Bile acids, bacteria, gallbladder stones

187
Q

Chronic Inflammatory States and Cancer:
Reflux esophagitis, Barrett esophagus

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Esophageal carcinoma

* Agent = Gastric acid

188
Q

Chronic Inflammatory States and Cancer:
Sjogren syndrome, Hashimoto thyroiditis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= MALT lymphoma

* Agent = —

189
Q

Chronic Inflammatory States and Cancer:
Opisthorchis, cholangitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Cholangiocarcinoma, colon carcinoma

* Agent = Liver flukes

190
Q

Chronic Inflammatory States and Cancer:
Gastritis/ulcers

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Gastric adenocarcinoma, MALT lymphoma

* Agent = Helicobacter pylori

191
Q

Chronic Inflammatory States and Cancer:
Hepatitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Hepatocellular carcinoma

* Agent = Hep B and/or C virus

192
Q

Chronic Inflammatory States and Cancer:
Osteomyelitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Carcinoma in draining sinuses

* Agent = Bacterial infection

193
Q

Chronic Inflammatory States and Cancer:
Chronic cervicitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Cervical carcinoma

* Agent = Human papillomavirus

194
Q

Chronic Inflammatory States and Cancer:
Chronic cystitis

  • Neoplasm=
  • Agent =
A
  • Neoplasm= Bladder carcinoma

* Agent = Schistosomiasis

195
Q

Agents associated with Lung Carcinoma?

A
  • Arsenic
  • Asbestos
  • Beryllium
  • Chromium (not cadmium, which is prostate)
  • Nickel
  • Radon
196
Q

Precursor Lesions and their Link to Malignancy

A
  1. ) Chronic Inflammation (can be recognized by the presence of metaplasia):
    - BARRETT ESOPHAGUS (gastric and colonic metaplasia of the esophageal mucosa in the setting of gastric reflux);
    - SQUAMOUS METAPLASIA of the BRONCHIAL MUCOSA (in response to smoking) and the BLADDER MUCOSA (in response to schistosomiasis infection)
    - COLONIC METAPLASIA OF THE STOMACH (in the setting of pernicious anemia and chronic atrophic gastritis).
  2. ) Noninflammatory Hyperplasias:
    - One of the most common precursor lesions of this type is ENDOMETRIAL HYPERPLASIA , which is caused by sustained estrogenic stimulation of the endometrium.
    - Another relatively frequent precursor lesion is LEUKOPLAKIA, a thickening of squamous epithelium that may occur in the oral cavity or on the penis or vulva and give rise to squamous carcinoma.
  3. ) Benign Neoplasms (at risk for malignant transformation)
    - The classic example of a neoplastic precursor lesion is the COLONIC VILLOUS ADENOMA, which if left untreated progresses to cancer in about 50% of cases.
197
Q

Sporadic malignant neoplasms constitute roughly ?% of cancers in the United States

A

95%

198
Q

Ex. of Genetic Cancer with Environmental Influence

A

BREAST CANCER risk in females who inherit mutated copies of the BRCA1 or BRCA2 tumor suppressor genes is almost threefold higher for women born after 1940 than for women born before that year, perhaps because of changes in REPRODUCTIVE history.

199
Q

Ex. of Environmental Cancer with Genetic Influence

A
  • Inherited variations (polymorphisms) of enzymes that metabolize procarcinogens to their active carcinogenic forms can influence cancer susceptibility. Of interest in this regard are genes that encode the CYTOCHROME P-450 ENZYMES.
  • A polymorphism in one of the P-450 loci confers an inherited sus­ceptibility to LUNG CANCERS in cigarette smokers. More associations of this type are likely to be found.
200
Q

Most common Lung Cancer?

A
  1. ADENOCARCINOMA (38%)
  2. Squamous cell carcinoma
  3. Small cell carcinoma
  4. Large cell carcinoma
  5. Other
201
Q

The most common cancers overall are those of the ? **

A
  • Skin (Basal cell carcinoma)
  • Lung (Adenocarcinoma)
  • Large Bowel (Adenocarcinoma)
  • Prostate (Acinar Adenocarcinoma)
  • Breast (Invasive Ductal Carcinoma- aka Adenocarcinoma)
  • Cervix (Squamous cell carcinoma)
  • Oral cavity (Squamous cell carcinoma)
  • Bladder (Carcinoma - Transitional Cell Cancer)
202
Q

What is the most common general category of malignant tumor of adults in the US?

A

Carcinoma

203
Q

Most common Breast Cancer?

A

Invasive Ductal Carcinoma of the breast

204
Q

Stepwise acquisition of mutations in development of cancer

A

Look at Fig 7-22

  • Initiating mutation –> Acquisition of genomic instability
  • -> Acquisition of cancer hallmarks –> Further genetic evolution **
  • Normal cell –> Initiated precursor with stem cell-like properties (carcinogen-induced mutation) –> Precursor with mutator phenotype (Mutation affecting genomic integrity) –> Founding cancer cell (Additional driver mutations) –> Genetically heterogenous cancer (Additional mutations, Emergence of subclones)
205
Q

Stepwise acquisition of mutations in development of cancer

A
  • The first driver mutation that starts a cell on the path to malignancy is the INITIATING MUTATION , which is typically maintained in all of the cells of the subsequent cancer. However, because no single mutation appears to be fully transforming, development of a cancer requires that the “initiated” cell acquire a number of additional driver mutations, each of which also contributes to the development of the cancer.
  • LOSS-OF-FUNCTION mutations in genes that maintain genomic integrity appear to be a common early step on the road to malignancy, particularly in solid tumors . Mutations that lead to GENOMIC INSTABILITY not only increase the likelihood of acquiring driver mutations, but also greatly increase the frequency of mutations that have no phenotypic consequence, so-called passenger mutations, which are much more common than driver mutations.
  • Once established, tumors EVOLVE GENETICALLY during their outgrowth and progression under the pressure of Darwinian selection (survival of the fittest).
  • Selection of the fittest cells can explain not only the natural history of cancer, but also CHANGES IN TUMOR BEHAVIOR FOLLOWING THERAPY. One of the most profound selective pressures that cancer cells face is effective chemotherapy or radiotherapy given by treating physicians. Tumors that recur after therapy are almost always found to be RESISTANT if the same treatment is given again.
  • It is increasingly apparent that in addition to DNA mutations, EPIGENETIC ABERRATIONS also contribute to the malignant properties of cancer cells. Epigenetic modifications include DNA METHYLATION, which tends to silence gene expression, and MODIFICATIONS OF HISTONES, the proteins that package DNA into chromatin, which depending on their nature may either enhance or dampen gene expression. Together, DNA methylation and histone modifications dictate which genes are expressed, which in turn determines the lineage commitment and differentiation state of both normal and neoplastic cells.
206
Q

MYC

A
  • Proto-oncogene
  • Activation by translocation
  • Associated with Burkitt lymphoma
207
Q

NMYC

A
  • Proto-oncogene
  • Activated by amplification
  • Associated with neuroblastoma
208
Q

ERBB1 (EGFR)

A
  • Proto-oncogene
  • Activated by mutation
  • Associated with adenocarcinoma of lung
209
Q

ERBB2 (HER)

A
  • Proto-oncogene
  • Activated my amplification
  • Associated with breast carcinoma
210
Q

ALK

A
  • Proto-oncogene
  • Activated by translocation, fusion gene formation; point mutation
  • Associated with adenocarcinoma of the lung, certain lymphomas; Neuroblastoma
211
Q

ABL

A
  • Proto-oncogene
  • Activated by translocation or point mutation
  • Associated with chronic myelogenous leukemia and acute lymphoblastic leukemia
212
Q

CDK4

A
  • Proto-oncogene
  • Amplification or point mutation
  • Associated with glioblastoma, melanoma, sarcoma
213
Q

BRAF

A
  • Proto-oncogene
  • Activated by point mutation, translocation
  • Associated with melanomas, leukemias, colon carcinoma, etc.
214
Q

RB gene

A
  • Protein is retinoblastoma
  • Inhibitor of G1/S transition during cell cycle progression
  • Associated with familial and sporadic retinoblastoma, osteosarcoma, carcinoma of breasts, colon, lung
215
Q

TP53 **

A
  • P53 protein
  • Causes cell cycle arrest and apoptosis in response to DNA damage
  • Associated with familial Li-Fraumeni syndrome and most sporadic cancers
216
Q

VHL

A
  • Encodes a component of a ubiquitin ligase that is responsible for degradation of hypoxia-induced factors (HIFs), transcription factors that alter gene expression in response to hypoxia
  • Germline loss-of-function mutations cause von Hippel-Lindau syndrome which causes a high risk of renal cell carcinoma and pheocromocytoma
217
Q

NOTCH1

A
  • Proto-Oncogene
  • Activated by Point mutation, Translocation; Gene rearrangement
  • Associated with Leukemias, Lymphomas, Breast carcinoma
218
Q

JAK/STAT signal transduction

A
  • Proto-Oncogene
  • Activated by Translocation
  • Associated with Myeloproliferative disorders and Acute lymphoblastic leukemia
219
Q

PDGF - B chain

A
  • Proto-oncogene
  • Activated by overexpression
  • Associated with Astrocytoma
220
Q

Form a complex that phosphorylates RB, allowing the cell to progress through the G1 restriction point

A

CDK4; D cyclins (cyclins and cyclin-dependent kinases)

221
Q
  • Block the cell cycle by binding to cyclin-CDK complexes
  • p21 is induced by the tumor suppressor p53
  • p27 responds to growth suppressors such as TGF-B
A

CIP/KIP family: p21, p27 (cell cycle inhibitor)

222
Q
  • p16/INK4a binds to cyclin D-CDK4 and promotes the inhibitory effects of RB
  • p14/ARF increases p53 levels by inhibiting MDM2 activity
A

INK4/ARF family (cell cycle inhibitor)

223
Q

Tumor Suppressor Genes:
APC

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Familial colonic polyps and carcinomas

•Sporadic Cancers
- Carcinomas of stomach, colon, pancreas; melanoma

224
Q

Tumor Suppressor Genes:
NF1

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Neurofibromatosis type 1 (neurofibromas and malignant peripheral nerve sheath tumors)

•Sporadic Cancers
- Neuroblastoma, juvenile myeloid leukemia

225
Q

Tumor Suppressor Genes:
PTCH

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Gorlin syndrome (basal cell carcinoma, medulloblastoma, several benign tumors)

•Sporadic Cancers

  • Basal cell carcinoma
  • Medulloblastoma
226
Q

Tumor Suppressor Genes:
VHL

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Von Hippel Lindaus syndrome (cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma)

•Sporadic Cancers
- Renal cell carcinoma

227
Q

Tumor Suppressor Genes:
CDH1

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Familial gastric cancer

•Sporadic Cancers

  • Gastric carcinoma
  • Lobular breast carcinoma
228
Q

Tumor Suppressor Genes:
BRCA1, BRAC2

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Familial breast and ovarian carcinoma; carcinomas of male breast; chronic lymphocytic leukemia (BRCA2)

•Sporadic Cancers
- Rare

229
Q

Tumor Suppressor Genes:
MSH

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Hereditary nonpolyposis colon carcinoma

•Sporadic Cancers
- Colonic and endometrial carcinoma

230
Q

Tumor Suppressor Genes:
WT1

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Familial Wilms tumor

•Sporadic Cancers
- Wilms tumor, certain leukemias

231
Q

Tumor Suppressor Genes:
NF2

  • Familial Syndromes = ?
  • Sporadic Cancers = ?
A

• Familial Syndromes
- Neurofibromatosis type 2 (acoustic shwannoma and meningioma)

•Sporadic Cancers

  • Schwannoma
  • Meningioma
232
Q

Immunotherapy Markers?

A
  • PD-L1
  • CTLA-4
  • PDE4
233
Q
  • Cancer cells demonstrate a distinctive form of cellular metabolism characterized by high levels of glucose uptake and increased conversion of glucose to lactose (fermentation) via the glycolytic pathway
  • Aerobic glycolysis
  • It provides rapidly dividing tumor cells with metabolic intermediates that are needed for the synthesis of cellular components, whereas mitochondrial oxidative phosphorylation does not
  • Metabolic reprogramming is produced by signaling cascades downstream of growth factor receptors, the very same pathways that are deregulated by mutations in oncogenes and tumors suppressor genes in cancers
  • Ex: PI3K/AKT, RTK’s activity, MYC
A

Warburg Effect

234
Q
  • Abnormalities in both intrinsic and extrinsic pathways are found in cancer cells. Intrinsic most common
  • 85% of follicular B-cell lymphomas anti-apoptotic BCL2 is overexpressed due to translocation
  • Overexpression of MCL-1 is also linked to cancer cell survival and drug resistance
A

Evasion of Apoptosis

235
Q
  • At least some cells in all cancers must be stem-like
  • May arise through transformation of normal stem cell or through acquired genetic lesions
  • Cancer cells acquire lesions that inactivate senescence signals and reactivate telomerase, which act together to convey limitless replicative potential
A

Stem-cell like properties

236
Q
  • Vascularization of tumors is essential for their growth and is controlled by the balance between angiogenic and anti-angiogenic factors that are produced by tumor and stromal cells
  • Hypoxia triggers angiogenesis through HIF-1a which stimulates VEGF
  • P53 dowregulates VEGF
  • RAS, MYC, and MAPK upregulate VEGF
  • VEGF inhibitors are used to treat a number of advanced cancers and prolong the clinical course, but are not curative
A

Angiogenesis

237
Q
  • Immune system recognizes tumors as non-self and can destroyed
  • Antitumor activity mediated mainly by CD8+ CTLs
  • Tumor antigens include products like mutated proto-oncogenes, tumor suppressor genes, aberrant expressed proteins, altered glycolipids and glycoproteins
  • Immunosuppressed patients have an increased risk for development of cancer, particularly by oncogenic DNA viruses
  • Tumor may evade immune system by mechanisms like: selective outgrowth of antigen-negative variants, loss or reduced expression of HLA, by suppression of molecules (TGF-b, PD-1 ligand, galectins)
A

Evasion of immune surveillance

238
Q
  • Persons with inherited mutations of genes involved in DNA repair are at greater risk for cancer
  • HNPCC syndrome have defects in the mismatch repair system , leading to development of carcinomas of the colon
  • Patients with xeroderma pigmentosum have a defect in the nucleotide excision repair pathway and are at increased risk for skin cancer (inability to repair pyrimidines)
  • Syndromes involving defects in the homologous recombination DNA repair system constitute a group of disorders (Bloom syndrome, ataxia-telengiectasia, and Fanconi anemia) that are characterized by hypersensitivity to DNA-damaging agents such as ionizing radiation. Ex: BRCA1 and BRCA2
  • Mutations incurred in lymphoid cells due to expression of gene products that induce genomic instability (RAG1, RAG2, AID) are important causes of lymphoid neoplasms.
A

Genomic instability

239
Q
  • Infiltrating cancers produce a chronic inflammation
  • In advanced cancers it can be so extensive as to cause systemic signs and symptoms, such as anemia
  • Anemia is caused due to inflammation-induced sequestration of iron and downregulation of erythropoietin production
  • Cause also fatigue and cachexia
  • Inflammatory cells also modify the local tumor microenvironment to enable many of the hallmarks of cancer
  • These effects may stem from direct interactions between inflammatory cells and tumor cells on other resident stromal cells, particularly cancer-associated fibroblast and endothelial cells.
A

Cancer-enabling inflammation

240
Q
  • Tumor cells may acquire several types of oncogenic mutations
  • Balanced translocations contribute to carcinogenesis by overexpression of oncogenes or generation of novel fusion proteins with altered signaling capacity
  • Genomic sequencing has revealed numerous “cryptic” (subcytogenic) rearrangements, mainly small deletions and insertions (“indels”), as well as chromothrypsis, in which a chromosome is “shattered” and then reassembled in a haphazard way.
A

Dysregulation of cancer-associated genes

241
Q

Molecular Basis of Multi-Step Carcinogenesis

A
  1. APC at 5q21: Germ-line (inherited) or somatic (acquired) mutations of cancer suppressor genes (“first hit”)
  2. APC B-catenin: Methylation abnormalities. Inactivation of normal alleles (“second hit”)
  3. K-RAS at 12p12: Proto-oncogene mutations

Now 2 different paths

4A. Wild-type TP53: Oncogene-induced senescence

4B. TP53 at 17p13. LOH at 18q21 (SMAD 2 and 4): Homozygous loss of additional cancer suppressor genes
–> 5. Telomerase. Many other genes.: Additional mutations. Gross chromosomal alterations.

242
Q

What are the 2 big categories in the Steps of Chemical Carcinogenesis?

A
  1. Initiation
  2. Promotion

Promotors cause clonal expansion of the initiated cell, thus producing a preneoplastic clone. Further proliferation induced by the promoter or other factors causes accumulation of additional mutations and emergence of a malignant tumor

243
Q

Chemical Carcinogenesis:

Causes permanent DNA damage (mutations); it is therefore rapid and irreversible and has “memory”

A

Initiation

244
Q

Chemical Carcinogenesis:

Can induce tumors to arise from initiated cells, but they are nontumorigenic by themselves

A

Promotors

245
Q

Steps of Chemical Carcinogenesis?

A

Initiation:

  1. Carcinogen
    - Side path: Detoxification then Excretion
  2. Electrophilic Intermediates
    - Side path: Detoxification then Excretion
  3. Binding to DNA: Adduct formation
    - Side path: Either goes through DNA repair and becomes a normal cell OR undergoes cell death
  4. Permanent DNA lesion: Initiated cell

Promotion:
5. Cell proliferation: Altered differentiation

  1. Preneoplastic clone - undergoes proliferation and additional mutations
  2. Malignant Neoplasm
246
Q

Chemical Carcinogenesis:

  • Require no metabolic conversion to become carcinogenic
  • Most are weak carcinogens but some are important because they are cancer chemotherapeutic drugs (alkylating agents)
  • Sadly in some instances, these agents have successfully cured, controlled, or delayed recurrence of certain types of cancer (e.g. leukemia, lymphoma, and ovarian carcinoma) only to evoke later a second form of cancer, usually acute myeloid leukemia
A

Direct-acting Carcinogens

247
Q

Chemical Carcinogenesis:

  • Chemicals that require metabolic conversion to become active carcinogens (ultimate carcinogen)
  • Most potent = Polycyclic hydrocarbons present in fossil fuels or animal fats
  • Others = benzo pyrene are formed during high temperature combustion of tobacco in cigarettes and implicated in the causation of lung cancer
  • Also include aromatic amines and azo dyes
  • Most known carcinogens are metabolized by cytochrome P-450 dependent mono-oxygenases
A

Indirect-acting carcinogen

248
Q

Chemical Carcinogenesis:

Molecular Targets

A
  • mutations occur throughout the genome and cells that by chance suffer damage to the usual oncogenes and tumor suppressors like RAS and TP53
  • some interact preferentially with particular DNA sequences or bases and thus produce mutations that are clustered at “hot spots”or that are enriched for particular base substitutions (ex. Aflatoxin B1 produced by mold Aspergillus that grows on grains and nuts)
249
Q

Radiation Carcinogenesis:

Exposure to UV rays derived from the sun, esp in fair skinned people, is associated with an increased incidence of ?

A
  • Squamous cell carcinoma, Basal cell carcinoma, and melanoma of the skin
250
Q

Radiation Carcinogenesis:

  • UV can be divided into what 3 wavelength ranges?
  • Which of these is believed to be responsible for the induction of cutaneous cancers?
  • Which is not considered significant because it is filtered out by the ozone layer?
A
  • UVA (320-400nm)
  • UVB (280-320 nm)
  • UVC (200-280nm)
  • UVB
  • UVC
251
Q

Radiation Carcinogenesis:

The carcinogenicity of UVB light is due to formation of ? in DNA

A

Pyrimidine Dimers (usually thymidine)

252
Q

Radiation Carcinogenesis:

The importance of the nucleotide excision repair pathway of DNA repair is illustrated by the high frequency of cancers in individuals with the hereditary disorder ?

A

Xeroderma Pigmentosum

253
Q

Radiation Carcinogenesis: Ionizing Radiation

  • Electromagnetic (x rays, y rays) and particulate (alpha particles, B particles, protons, neutrons) radiations are all carcinogenic
  • Miners of radioactive elements have a 10 fold increase in?
  • Survivors of atomic bombs have increase in?
  • Currently, ? scans are of interest. Studies show that children who get 2-3 CT scans have a threefold higher risk of ?, and 5-10 scans have a threefold higher risk of ?
A
  • Lung cancer
  • Leukemia
  • CT
  • Leukemia
  • brain tumors
254
Q

Radiation Carcinogenesis:

- Hierarchy of vulnerability of different tissues to radiation induced cancers

A
  1. Myeloid Leukemia
  2. Cancers of Thyroid (only in young)
  3. Cancers of the Breast, Lung, Salivary Gland

In contrast, skin, bone, and GI are resistant to radiation-induced neoplasia

255
Q

Microbial Carcinogenesis:

Oncogenic RNA Viruses:

  • Associated cancer?
  • Important gene associated?
A
  • HTLV-1 (Human T cell Leukemia Virus Type 1) causes ADULT T CELL LEUKEMIA/LYMPHOMA (ATLL), a tumor that is endemic in certain parts of Japan, the Caribbean basin, South America, and Africa, and found sporadically elsewhere including the US
  • Infection requires transmission of infected T cells via sexual intercourse, blood products, or breast feeding
  • In contrast to other retroviruses, it does not contain an oncogene
  • Random integration site
  • In contrast to all other leukemia viruses, it contains another gene referred to as Tax *** which attributes to several of HTLV-1’s transforming activity
  • Tax increases pro-growth signaling and cell survival with interaction with PI3K and stimulates AKT. It also increases genomic instability
256
Q

Microbial Carcinogenesis:

Oncogenic DNA Viruses: HPV

  • Associated cancer?
  • Important Genes?
A
  • Some types cause BENIGN SQUAMOUS PAPILLOMAS (warts) in humans. in contrast, high risk HPVs (16 and 18) have been implicated in the genesis of SQUAMOUS CELL CARCINOMAS of the cervix, anogenital region, and head and neck
  • Random integration site but pattern of integration is clonal
  • get loss of the E2 viral repressor and over expression of the oncogenes E6 (mediates degradation of p53 and stimulates TERT which is used for immortalization of cells) and E7 **
257
Q

Microbial Carcinogenesis:

Oncogenic DNA Viruses: Epstein-Barr Virus (EBV)

  • Associated cancer?
A
  • African form of BURKITT LYMPHOMA (100% of patients have elevated antibody titers against viral capsid antigens. EBV is NOT directly oncogenic)
  • B cell lymphomas in immunosuppressed individuals (EBV is more DIRECT)
  • A subset of Hodgkin lymphoma
  • Nasopharyngeal and some gastric carcinomas
  • Rare forms of T-cell lymphoma and natural killer cell lymphoma
  • Most common EBV associated tumors are derived from B cells and nasopharyngeal carcinoma
  • In the absence of T cell immunity, EBV- infected B cells can rapidly “grow out” as aggressive B-cell tumors
  • In the presence of normal T cell immunity, a small fraction of infected patients develop EBV-positive B- cell tumors (Burkitt lymphoma, Hodgkin lymphoma) or carcinomas (nasopharyngeal, gastric carcinoma)
258
Q

Microbial Carcinogenesis:

Oncogenic DNA Viruses: Hep B (HBV) and C (HCV)

  • Associated cancer?
A
  • Cancer = Hepatocellular Carcinoma
  • Oncogenic effects are multifactorial; dominant effect seems to be immunologically mediated chronic inflammation, hepatocellular injury, and reparative hepatocyte proliferation
  • HBx protein of HBV and the HCV core protein can activate signal transduction pathways that also may contribute to cracinogenesis
259
Q

Microbial Carcinogenesis:

Oncogenic DNA Viruses: H.pylori

  • Associated cancer?
A
  • Cancer = gastric adenocarcinoma and MALT lymphoma
  • Pathogenesis of H. pylori- induced gastric cancers is multifactorial, including chronic inflammation and reparative gastric cell proliferation
  • H. pylori pathogenicity genes, such as CagA, also may contribute by stimulating growth factor pathways
  • Chronic H. pylori infection leads to polyclonal B-cell proliferations that may give rise to a monoclonal B-cell tumor (MALT lymphoma) of the stomach as a result of accumulation of mutations
260
Q

Local and Hormonal Effects of Cancer

A
  • location is a critical determinant of the clinical effects of both benign and malignant tumors
  • Tumors may impinge upon vital tissues and impair their functions, cause death of involved tissues and provide a nidus for infection
  • Cancers arising within or metastatic to an endocrine gland may cause an endocrine insufficiency by destroying the gland
  • Neoplasms in the gut, both benign and malignant, may cause obstruction as they enlarge
  • Infrequently, peristaltic movement telescopes the neoplasm and its affected segment into the downstream segment, producing an obstructing intussusception
  • Benign and malignant neoplasms arising in endocrine glands can cause clinical problems by producing hormones
  • The erosive and destructive growth of cancers or the expansile pressure of a benign tumor on any natural surface, such as the skin or mucosa of the gut, may cause ulcerations, secondary infections, and bleeding
  • Melena (blood in the stool) and hematuria, for example, are characteristic of neoplasms of the gut and urinary tract
261
Q

Individuals with cancer commonly suffer progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia, and anemia, referred to as ?

A

Cachexia

262
Q

Cancer cachexia is associated with ?

A
  • Equal loss of both fat and lean muscle
  • Elevated basal metabolic rate
  • Evidence of systemic inflammation (e.g., an increase in acute phase reactants)
263
Q

Cancer Cachexia

  • Which mediator is released from immune cells and may contribute to cachexia?
  • Humoral factors released from tumor cells such as ? have been implicated in the loss of muscle mass
A
  • TNF-alpha

- proteolysis inducing factor

264
Q

Some cancer bearing individuals develop signs and symptoms that cannot readily be explained by the. anatomic distribution of the tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose. These are known as ?

A

Paraneoplastic Syndromes

265
Q

Paraneoplastic Syndromes:

What is the most common endocrinopathy?

A

Cushing Syndrome

  • 50% have small cell carcinoma of the lung
  • It is caused by excessive production of corticotropin
266
Q

Paraneoplastic Syndromes:

What is the most common Paraneoplastic Syndrome?

A

Hypercalcemia

  • 2 general processes involved in cancer-associated hypercalcermia:
    1. Osteolysis
    2. Production of calcemic humoral substances by extraosseous neoplasms
267
Q

Paraneoplastic Syndromes:

Disorder characterized by gray-black patches of thickened, hyperkeratotic skin with a velvety appearance

A

Acanthosis nigricans

268
Q

Paraneoplastic Syndromes:

Disorder characterized by:
1. Periosteal new bone formation, primarily at the distal ends of long bones, metatarsals, metacarpals, and proximal phalanges

  1. Arthritis of the adjacent joints
  2. Clubbing of the digits
A

Hypertrophic Osteoarthropathy

269
Q

Paraneoplastic Syndromes:

Endocrinopathies: Cushing Syndrome **

  • Cancer = ?
A
  • Small cell carcinoma of lung
  • Pancreatic carcinoma
  • Neural tumors
270
Q

Paraneoplastic Syndromes:

Endocrinopathies: Syndromes of inappropriate antidiuretic hormone secretion

  • Cancer = ?
A
  • Small cell carcinoma of lung

- Intracranial neoplasms

271
Q

Paraneoplastic Syndromes:

Endocrinopathies: Hypercalcemia **

  • Cancer = ?
A
  • Squamous cell carcinoma of lung
  • Breast carcinoma
  • Renal carcinoma
  • Adult T cell leukemia/lymphoma

(causal mechanism = Parathyroid hormone related protein aka PTHRP)

272
Q

Paraneoplastic Syndromes:

Endocrinopathies: Hypoglycemia

  • Cancer = ?
A
  • Ovarian carcinoma
  • Fibrosarcoma
  • Other mesenchymal sarcomas
273
Q

Paraneoplastic Syndromes:

Endocrinopathies: Polycythemia

  • Cancer = ?
A
  • Renal carcinoma
  • Cerebellar hemangioma
  • Hepatocellular carcinoma
274
Q

Paraneoplastic Syndromes:

Nerve and Muscle Syndromes: Myasthenia

  • Cancer = ?
A
  • Bronchogenic carcinoma

- Thymic neoplasms

275
Q

Paraneoplastic Syndromes:

Nerve and Muscle Syndromes: Disorders of the central and peripheral nervous system

  • Cancer = ?
A
  • Breast carcinoma
276
Q

Paraneoplastic Syndromes:

Dermatologic Disorders: Acanthosis nigricans

  • Cancer = ?
A
  • Gastric carcinoma
  • Lung carcinoma
  • Uterine carcinoma
277
Q

Paraneoplastic Syndromes:

Dermatologic Disorders: Dermatomyositis

  • Cancer = ?
A
  • Bronchogenic carcinoma

- Breast carcinoma

278
Q

Paraneoplastic Syndromes:

Osseous, Articular, and Soft Tissue Changes: Hypertrophic osteoarthropathy and clubbing of the fingers

  • Cancer = ?
A
  • Bronchogenic carcinoma

- Thymic neoplasms

279
Q

Paraneoplastic Syndromes:

Vascular and Hematologic Changes: Venous Thrombosis (Trousseau phenomenon)

  • Cancer = ?
A
  • Pancreatic carcinoma
  • Bronchogenic carcinoma
  • Other cancers
280
Q

Paraneoplastic Syndromes:

Vascular and Hematologic Changes: Disseminated intravascular coagulation

  • Cancer = ?
A
  • Acute promyelocytic leukemia

- Prostate carcinoma

281
Q

Paraneoplastic Syndromes:

Vascular and Hematologic Changes: Nonbacterial thrombotic endocarditis

  • Cancer = ?
A
  • Advanced cancers
282
Q

Paraneoplastic Syndromes:

Vascular and Hematologic Changes: Red cell aplasia

  • Cancer = ?
A
  • Thymic neoplasms
283
Q

Paraneoplastic Syndromes:

Others: Nephrotic syndrome

  • Cancer = ?
A
  • Various cancers
284
Q

Determined by cytologic appearance; based on the idea that behavior and differentiation are related, with poorly differentiated tumors having more aggressive behavior

A

Grading

285
Q

Determined by surgical exploration or imaging, is based on size, local and regional lymph nodes spread, and distant metastases; of greater clinical value than grading

A

Staging

286
Q

What is grading based on?

A

Based on the degree of differentiation of the tumor cells and in some cancers, the number of mitoses or architectural figures

287
Q
  • 2 categories of grading?

- What descriptive terms are used to characterize a particular neoplasm?

A
  • Low grade and high grade

- Well-differentiated or poorly differentiated

288
Q

Staging of solid tumors is based on?

A
  • the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases
289
Q

Staging System of Classification is called?

A

TNM System

  • T = for primary tumor
  • N = for regional lymph node involvement
  • M = for Metastases
290
Q

TNM System:
- The primary lesion is characterized as ? based on increasing size.

  • T0 is used to indicate?
A
  • T1 to T4

- An in situ lesion

291
Q

TNM System:

  • N0 would mean?
  • ? would denote involvement of an increasing number and range of nodes
A
  • No nodal involvement

- N1 to N3

292
Q

TNM System:

  • M0 signifies ?
  • ? indicates the presence of metastases and some judgement as to their number
A
  • no distant metastases

- M1 or sometimes M2

293
Q

Lab Diagnosis of Cancer:

What are the 3 Histologic and Cytologic Methods?

A
  1. Excision or biopsy
    - can request “quick frozen section” diagnosis can be used in determining the nature of a mass lesion, in evaluating margins of an excised cancer to ascertain that an entire neoplasm has been removed, or in making decisions about what studies beyond histo are needed. Permits histo eval in minutes
  2. Fine-needle aspiration
    - Most common for the assessment of readily palpable lesions in sites like the breast, thyroid, and lymph nodes
    - Less invasive and more rapidly performed than needle biopsies
  3. Cytologic smears
    - Widely used in the screen for CARCINOMA OF THE CERVIX (often at an in situ stage)
    - Ex. Pap smears
294
Q

Lab Diagnosis of Cancer:

Immunohistochemistry can be used for?

A
  • Categorization of undifferentiated malignant tumors
  • Determination of site of origin of metastatic tumors
  • Detection of molecules that have prognostic or therapeutic significance
295
Q

Lab Diagnosis of Cancer:

  • What is Flow Cytometry used for?
  • Advantage of Flow Cytometry over Immunohistochemistry?
A
  • Used to identify cellular antigens expressed by “liquid” tumors, those that arise from blood-forming tissues
  • These include B- and T-cell lymphomas and leukemias, as well as myeloid neoplasms
  • Advantage: Multiple antigens can be assessed simultaneously on individual cells using combinations of specific antibodies linked to different fluorescent dyes
296
Q

Lab Diagnosis of Cancer:

Diagnostic Modality of Circulating tumor Cells

A

Instrumentation that permits detection, quantification, and characterization of rare solid tumor cells (e.g., carcinoma, melanoma) circulating in the blood

297
Q

Lab Diagnosis of Cancer:

Molecular and Cytogenic Diagnostics can be used for ?

A
  1. Diagnosis of malignant neoplasms:
    - PCR-based eval of rearranged T-cell receptor or immunoglobulin genes allows distinction between monoclonal (neoplastic) and polyclonal (reactive) proliferations
    - DNA microarrays - allow high-resolution mapping of copy number changes (either deletions or amplifications) genome-wide
  2. Prognosis of malignant neoplasms:
    - Certain genetic alterations are associated with poor prognosis, and hence their detection allows stratification of patients for therapy
  3. Detection of minimal residual disease:
    - PCR-based amplification of nucleic acid sequences unique to the malignant clone
  4. Diagnosis of hereditary predisposition to cancer:
    - Such analysis usually requires detection of a specific mutation or sequencing of the entire gene
  5. Guiding therapy with oncoprotein-directed drugs:
    - An increasing number of of chemotherapeutic agents target oncoproteins that are only present in a subset of cancers of a particular type
    - Thus, the molecular identification of genetic lesions that produce these oncoproteins is essential for optimal treatment of patients
298
Q

Future of Cancer Diagnostics

A
  • At present, using NextGen sequencing, certain cancer centers are completing the process of whole genome sequencing for individual tumors in 28 days, which includes the time required for the complex task of assembling and analyzing the sequencing data
  • CIRCOT PLOT - provide a snapshot of all of the genetic alterations that exist in a particular tumor
  • The current trend in molecular diagnostic labs is to develop methods that permit several hundred exons of key genes to be sequenced simultaneously at sufficient “depth” to reliably detect any mutations that might be present in as few as 5% of tumor cells
  • A second method moving rapidly into clinical practice involves the use of DNA ARRAYS to identify changes in DNA copy number, such as amplification and deletions
  • Histopathologically, distinct cancers all often harbor the same gain of function mutation in the serine/threonine kinase BRAF, a component of the RAS signaling pathway
  • BUT the effectiveness of BRAF inhibitors vary widely depending on histologic subtype (ex. hairy cell leukemia = sustained responses; melanomas =respond transiently, colon carcinomas = respond little)
  • Histopathology, coupled with in situ biomarker tests performed on tissue sections also remains the best way to assess tumor:stromal cell interactions, such as angiogenesis and host immune responses
  • For the foreseeable future the most accurate diagnosis and assessment of prognosis in cancer patients will be arrived at by a combination of morphologic and molecular techniques
299
Q

Genetic Complexity of Common Tumors (Fig 7-50-p336)

A
  • A circot plot showing genetic alterations in a single lung cancer male patient.
  • Each of the 24 chromosomes in the cancer is displayed in these chromosomes as follows
    A. Structural rearrangements in chromosomes. The blue lines denote intrachromosomal rearrangements, while the red lines denote interchromosomal rearrangements

B. Regions of loss of heterozygosity and allelic imbalance (overrepresentation of one allele versus the second) are in green

C. Copy number profiles, showing copy number losses (in red) and copy gains (in blue)

D. Point mutations, represented as red dots

300
Q

Tumor Markers

A

• Biochemical assays can’t be used for definitive diagnosis of cancer but can be used for detection

301
Q

Tumor Marker:

Prostate specific antigen (PSA) is for what cancer?

A
  • Prostatic adenocarcinoma (suspected when elevated levels of PSA are found in blood)
  • But PSA screening highlights problems encountered with virtually every tumor markers. Although PSA levels are often elevated in cancer, PSA levels are also elevated in benign prostatic hyperplasia
  • There is no PSA level that ensures that a person does not have prostate cancer
  • SO the PSA test has both LOW SENSITIVITY AND LOW SPECIFICITY
302
Q

Tumor Marker:

Carcinoembryonic antigen (CEA) is for what cancers?

A
  • Elaborated for carcinomas of the colon, pancreas, stomach, and breast, and lung
  • LACK BOTH SENSITIVITY AND SPECIFICITY
303
Q

Tumor Marker:

Alpha-fetoprotein (AFP) is for what cancers?

A
  • Produced by hepatocellular carcinomas, yolk sac remnants in the gonads, and occasionally teratomas and embryonal cell carcinomas
  • So liver cell cancer, nonseminomatous germ cell tumors of testis
  • LACK BOTH SENSITIVITY AND SPECIFICITY
304
Q

Tumor Marker:

Human chorionic gonadotropin (HCG) is for what cancer?

A
  • Testicular cancer

- Also Trophoblastic tumors, nonseminomatous testicular tumors

305
Q

Tumor Marker:

CA-125 is for what cancer?

A

Ovarian tumors

306
Q

Tumor Marker:

Immunoglobulin is for what cancer?

A

In multiple myeloma and other secretory plasma cell tumors

307
Q

Tumor Marker:

Some of the cell-free DNAs being evaluated as tumor markers include mutated APC, TP53, and RAS sequences in the stool of individuals with?

A

Colorectal carcinomas

308
Q

Tumor Marker:

Mutated RAS and TP53 and hypermethylated genes in the sputum of persons with ?

A

Lung cancer

309
Q

Tumor Marker:

Mutated TP53 and hypermethylated genes in the saliva of persons with ?

A

Head and neck cancers

310
Q

Tumor Marker:

Mutated TP53 in the urine of patients with?

A

Bladder cancer

311
Q

Tumor Marker:

TP53, RAS mutants in stool and serum associated with what cancer?

A

Pancreatic cancer

312
Q

LO 31 (my guess??): Most common cancers of each system

  • Skin =
  • Deep soft tissue/vascular =
  • Bone =
  • Brain =
  • Pituitary/pineal =
  • Oral Cavity, head and neck =
  • Salivary glands =
  • Thyroid =
  • Parathyroids =
  • Thymus=
  • Lung =
  • Heart=
  • Esophagus=
  • Gall bladder=
  • Spleen=
  • Regional lymph nodes=
  • Bone marrow/circulation=
  • Pancreas, exocrine=
  • Pancreas, endocrine=
  • Stomach=
  • Small bowel=
  • Large bowel=
  • Adrenals=
  • Kidney=
  • Bladder=
  • Testes=
  • Penis=
  • Prostate=
  • Breast=
  • Ovaries=
  • Female adnexa and uterus region, (including cervix) =
A
  • Skin = Basal cell carcinoma
  • Deep soft tissue/vascular = Sarcoma
  • Bone = Osteosarcoma
    (most common in kids= Rhabdomyosarcoma)
  • Brain = Glioblastoma
  • Pituitary/pineal = Carcinoma
  • Oral Cavity, head and neck = Squamous cell Carcinoma
  • Salivary glands = Carcinoma
  • Thyroid = Carcinoma
  • Parathyroids = Carcinoma
  • Thymus= Carcinoma
  • Lung = Adenocarcinoma
  • Heart= Sarcoma
  • Esophagus= Squamous cell carcinoma (But if Barret’s espophagus = Adenocarcinoma)
  • Gall bladder =Adenocarcinoma
  • Spleen= Hemangiosarcoma?? NONE for cancer!
  • Regional lymph nodes= Lymphoma
  • Bone marrow/circulation= Leukemia
  • Pancreas, exocrine= Adenocarcinoma
  • Pancreas, endocrine= Gastrinoma
  • Stomach= Adenocarcinoma
  • Small bowel= Adenocarcinoma
  • Large bowel= Adenocarcinoma
  • Adrenals= Adenocarcinoma
  • Kidney= Adenocarcinoma
  • Bladder= Carcinoma ** (transitional cell cancer)
  • Testes= Lymphoma?. GERM CELL TUMORS (seminomas, …many types)
  • Penis= Carcinoma
  • Prostate=Adenocarcinoma
  • Breast= Invasive Ductal Carcinoma (same thing as Adenocarcinoma)
  • Ovaries= Adenocarcinoma
  • Female adnexa and uterus region, (including cervix) = Carcinoma
  • Liver = Hepatocellular carcinoma
  • Cervix = squamous cell carcinoma
  • Endometrium = Adenocarcinoma
  • Note: If GI related, probs Adenocarcinoma (glandular things)

MOD Exam 2 (6 decks)

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