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Block 3 - Fundamentals and Heme > Neoplasia > Flashcards

Neoplasia Flashcards

0
Q

What does the word neoplasm mean?

A

New growth
Biological process of cellular outgrowth - group of cells that grows faster than and independent of its neighbors
A precancer that doesn’t yet form a tumor and can only be observed on microscope (cervical intraepithelial neoplasia - CIN)
Dysequilibrium where cell growth exceeds cell death

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1
Q

What does the word tumor mean?

A

A swelling or mass

Raises possibility of malignancy but doesn’t imply one

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2
Q

What is a cancer or malignancy?

A

A neoplastic process where cells have acquired ability to invade and/or metastasize and thus spread locally or systematically

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3
Q

What is contact inhibition?

A

Cells (like fibroblasts) will grow on a plate until they touch each other and then they will stop dividing
Neoplasms no longer responsive to this

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4
Q

What is the difference between hyperplasia and neoplasia?

A

Hyperplasia - overgrowth of tissue in response to stimulus for growth, occurs within framework of normal regulatory processes, stimulus removed and growth will stop, growth coordinated and approximately normal architecturally, polyclonal
Neoplasia - not normal regulatory mechanisms, clonal

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5
Q

What is the gray zone between hyperplasia and neoplasia?

A

Long standing hyperplasia may persist after removal of stimulus although growth ordered and stable (hyperparathyroidism)
Some neoplasms maintain dependence on hormonal or other growth stimuli (uterine leiomyomata - fibroids)

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6
Q

What is dysplasia?

A

Deranged growth
Abnormal cytoarchitecture and misarrangement of cells that can be seen under the microscope
Usually in reference to neoplastic processes but not always

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7
Q

What is epithelial dysplasia?

A

Loss of normal, progressive, maturational sequence accompanied by cellular atypia and loss of normal tissue organization
Dysplasias are true precancers - lesions at increased risk of progressing to invasive cancers
Most forms are neoplastic proliferations confined to epithelium

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8
Q

How are CIN lesions of epithelial dysplasia graded?

A

Low grade - more variation in size and shape of nuclei, some cells have >1 nuclei - will likely regress on its own
High grade - cells on basement membrane but loss of regular maturation, lots of mitotic bodies, chronic inflammatory infiltrate - high risk of progression to cancer

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9
Q

What does carcinoma in situ mean?

A

Lesion that histologically cannot be reliably distinguished from cancer cells but cells have not yet transgressed normal tissue boundaries like the basement membrane

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10
Q

What are benign epithelial tumors and what term is used to refer to them?

A

Adenomas
Term modified by tissue of origin (renal cell, liver cell, thyroid)
Some not completely benign but are true precancers
Term may be further modified by descriptors of appearance (mucinous cystadenoma or serous cystadenoma of ovary)
Exceptions - papillary glandular tumors called papilloma, polyps

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11
Q

How is papillary growth characterized?

A

Complex branching

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12
Q

What are some examples of papillomas?

A

Squamous cell papilloma of skin = skin tag
Transitional cell papilloma of bladder
Intraductal papilloma of breast

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13
Q

What are some examples to the benign epithelial tumor terminology?

A

Melanocytic Nevus/Nevus - benign tumor of dermal melanocytes
Mesothelioma - highly aggressive and malignant neoplasm derived from mesothelium
Hepatoma - hepatocellular carcinoma - not benign

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14
Q

What is the terminology to describe malignant epithelial tumors?

A

Carcinomas
From glandular epithelium - adenocarcinomas
Term may be modified by other descriptors (papillary adenocarcinoma of ovary, cystadenocarcinoma of ovary)
Sometimes lose adeno (renal cell carcinoma, colon carcinoma, hepatocellular carcinoma)

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15
Q

What are some examples of non glandular epithelial malignancies?

A

Reflect tissue of origin
Squamous cell carcinoma - skin
Basal cell carcinoma - skin
(Papillary) Transitional cell carcinoma - bladder
Choriocarcinoma - trophoblast cells of placenta

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16
Q

What are benign mesenchymal tumors and how are they referred to?

A

Mesenchyme= connective tissue, stroma, etc
Name generally reflects cell of origin followed by -oma
(Fibroma, lipoma, chondroma, osteoma, hemangioma, lymphangioma, leiomyoma (smooth muscle), rhabdomyoma (skeletal muscle), meningioma)

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17
Q

How are malignant mesenchymal tumors referred to?

A

Term sarcoma appended to cell of origin

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18
Q

What are some exceptions to the terms for referring to mesenchymal tumors?

A

Malignant schwannoma - malignant tumor of Schwann cells in peripheral nerves
Leukemia - tumor of white blood cells with circulating neoplastic cells
Lymphoma - tumor of white blood cells, forms masses in lymph nodes, may also have circulating neoplastic cells
Invasive meningioma - aggressive, invasive version of benign

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19
Q

What is seminoma?

A

Malignant tumor of germ cells, testicular cancer

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20
Q

What is a melanoma?

A

Malignant tumor of melanocytes

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21
Q

What is a carcinoid tumor?

A

Derived from neuroendocrine cells

Often arise in the gut

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22
Q

What are mixed or biphasic tumors?

A

Comprised of more than one neoplastic cell type

Two predominant components –> biphasic

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23
Q

What is a pleomorphic adenoma?

A

Mixed tumor of salivary gland with neoplastic epithelial and stromal elements
Benign
Modified by “malignant” means malignant form

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24
Q

What is a fibroadenoma of breast?

A

Mixed tumor comprising of neoplastic epithelial and stromal elements
Benign

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25
Q

What are some examples of malignant mixed tumors?

A

Wilms tumor
Mixed mullerian tumor
Cystosarcoma phylloides of breast

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26
Q

What are teratomas?

A

Tumors comprised of more than one germ layer
Derived from toti or multipotential cells (germ cell lineage)
Most often in gonads but can sometimes be in extra gonadal locations

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27
Q

What are some benign teratomas?

A

Mature teratoma
Dermoid cyst - common type of mature teratoma characterized by keratinaceous debris from desquamating squamous epithelial cells

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28
Q

What is an example of a malignant teratoma?

A

Immature teratoma

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29
Q

What is a hamartoma?

A

Malformation that resembles a neoplasm but actually results from focal maldevelopment of that organ
Consists of tissue normally found at that site
Example - pulmonary hamartoma composed of cartilage and bronchial epithelium
Benign by definition

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30
Q

What is a choristoma?

A

Tumor formed by maldeveloped tissue not normally found at that site
Also known as heterotopic or ectopic rest
Example - adrenal rest - harmless masses of adrenal tissue that can be present in vicinity of ovary or kidney
Benign by definition

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31
Q

What are the five qualities that can be used to distinguish between benign and malignant tumors?

A 
Demarcation
Induration
Differentiation
Rate of growth
Distant spread (metastasis)
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32
Q

How does demarcation help differentiate between a benign or malignant tumors?

A

Benign - sharp, distinct margins, freely movable by palpation, clearly visible boundary between normal and tumor tissue, often encapsulated
Malignant - ill defined margins, boundary between normal and tumor tissues indistinct, jagged or stellate configuration

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33
Q

What is the capsule in benign tumors made out of?

A

Dense collagen produced by fibroblasts in response to pressure from adjacent mass

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34
Q

What is the exception to the rules of demarcation in distinguishing a tumor?

A

Some malignant tumors grow slowly enough to have a capsule - look for small foci of penetration through it

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35
Q

How is induration used to distinguish between benign and malignant tumors?

A

Induration = firmness of tumor on palpation

Induration in a tumor suggests an invasive cancer

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36
Q

What is desmoplasia?

A

Abnormal stroma produced by a tumor
Fibroblasts recruited produce abnormal, densely collagenous stroma
Leads to induration

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37
Q

What is differentiation of a tumor?

A

The degree to which a tumor resembles the normal tissue cells from which it arose
Can be based on morphological or functional features
Generally differentiation inversely correlated with tumor aggressiveness

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38
Q

How can differentiation be used to distinguish between benign and malignant tumors?

A

Benign tumors very well differentiated - they have a modest genetic load
Malignant tumors - much wider range of differentiation, poorly differentiated typically have increased cellularity

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39
Q

What is pleomorphism?

A

Much more variability in size, shape, and other characteristics of cells and nuclei seen in tumors

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40
Q

What is hyperchromasia?

A

Tumor nuclei usually stain more darkly

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41
Q

What are the features of cells and nuclei seen in tumor cells?

A 
Pleomorphism 
Hyperchromasia
Higher nuclear to cytoplasmic ratio
Abnormal mitotic figures
Prominent nucleoli - increased rRNA synthesis
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42
Q

What are four specific components that can be identified when using functional differentiation to distinguish between benign and malignant tumors?

A

Mucin from glandular cells
Keratin from squamous cells
Hormones from endocrine cells
ECM from bone and cartilage cells

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43
Q

What is anaplasia and what are four features of it?

A

Backward growth - loss of differentiation, tumors with it associated with poor prognosis

  1. Total lack of tissue organization
  2. Extreme cell and nuclear pleomorphism
  3. Large, hyperchromatic, bizarre nuclei
  4. Numerous, often abnormal mitotic figures
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44
Q

How can rate of growth be used to distinguish between benign and malignant tumors?

A

Benign - grow slowly
Malignant - rapid growing, more variable
Rate of growth generally increases with tumor progression and is correlated with degree of differentiation

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45
Q

What are the four different routes of metastasis?

A 
Direct seeding
Lymphatic spread
Hematogenous spread
Transplantation
Different tumor types tend to metastasize in stereotypical patterns but there are variations
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46
Q

What is direct seeding?

A

Spread within a body via detachment and subsequent implantation in a physically contiguous manner
Example - ovarian cells undergo peritoneal seeding

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47
Q

How does lymphatic spread work?

A

Major mode of spread of carcinomas
Malignant cells enter lymphatics, drain to lymph nodes, and can proliferate
Can spread via lymphatic system or to blood stream through thoracic duct

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48
Q

Where do breast, lung, testis, and leg skin tumors typically spread first in lymphatic spread?

A

Breast - axillary nodes
Lung - hilar or peri bronchial nodes
Testis - paraaortic nodes
Leg skin - inguinal lymph nodes

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49
Q

How does hematogenous spread of tumors work?

A

Major mode of spread for sarcomas
Usually via venous system
Intestinal tumors tend to metastasize to liver via portal system whereas other visceral tumors tend to go to lungs via venous drainage

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50
Q

What are common sites of metastasis?

A

Lymph nodes
Lung
Liver
Bone
Brain and kidney less common but not rare
Rarely skeletal muscle, heart, or GI tract

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51
Q

How does transplantation of tumor cells work?

A

Certain med interventions like surgery or biopsy can give cells access to new territories
Biopsies and fine needle aspirations do this rarely

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52
Q

How must you obtain diagnostic tissue from a testicular mass?

A

Orchiectomy is only option - no biopsy
Testis surrounded by tough fibrous capsule which would be violated by biopsy and allow cells to seed scrotal sac and spread to peritoneum through inguinal canal

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53
Q

What is benign metastasizing leiomyomatosis?

A

Uterine leiomyoma can seed numerous tumors at distant sites (peritoneum or lungs)
Metastases grow slowly and generally don’t cause morbidity

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54
Q

How does tumor grading work?

A

Based solely on histological appearance
Less differentiated is higher grade
Usually low, intermediate, high or grades I-IV
sometimes not correlated no prognosis

55
Q

How does staging of tumors work?

A

Assessment of physical extent of disease of tumor spread

56
Q

What is the TNM system of grading?

A 
T = size of primary (t1, t2, t3, t4)
N = regional lymph node involvement (n1, n2, n3)
M = distant metastasis (m0, m1 where m1 means distant metastases present)
57
Q

What are the five stages that the TNM system of tumor grading corresponds to?

A

Stage 0 = carcinoma in situ
Stage I, II, III = higher numbers indicate more extensive disease, greater tumor size, or spread to adjacent structures
Stage IV = metastasis

58
Q

What are two additional variables which may be included in a staging system?

A

Depth of invasion in hollow viscera

Lab markers of tumor burden

59
Q

Which is a better predictor of clinical progression - grading or stage?

A

Stage

60
Q

What is the difference between embryonic stem cells and adult stem cells?

A

ESCs are totipotent
Adult are multipotent, occupy a niche that influences the balance between stem cell renewal, maintenance, and differentiation

61
Q

What is the hypothesis of cancer stem cells?

A

They are rare undifferentiated cells within tumor possibly occupying a niche
Capable of replenishing themselves or differentiating to form viable tumor

62
Q

How does conventional chemotherapy support the hypothesis of cancer stem cells?

A

It kills differentiated cells but not cancer stem cells
Not surprising that many tumors that shrink or disappear will eventually regrow
Research exploring stem cells as new targets for cancer therapy - notch, wnt, and hedgehog signaling pathways regulate adult stem cells

63
Q

What four classes of regulatory genes are the targets of genetic mutations in cancer?

A

Proto oncogenes
Tumor suppressor genes
Genes regulating apoptosis
Genes involved in DNA repair

64
Q

What are the six fundamental changes in cell physiology that dictate malignant phenotype?

A

Self sufficiency in growth signals - growth
Insensitivity to growth inhibitory signals - growth
Evasion of apoptosis - survival
Limitless replicative potential - unlimited survival
Development of sustained angiogenesis - survival
Ability to invade and metastasize - spread ones seed

65
Q

How do oncogenes typically act on a cellular level?

A

Dominantly - without regard to status of proto oncogene counterpart in cell

66
Q

What components can regulation of cell proliferation by growth factors be broken down into?

A

Binding of growth factors to membrane receptors
Activated receptors activate signal transduction proteins
Transmission of signal from cytosol to nucleus
Activation of regulatory factors initiating DNA transcription
Entry and progression of cell into cell cycle

67
Q

What two ways can growth factor receptors promote tumorigenesis?

A
  1. Genetic mutation within protein sequence itself causes receptor to have exuberant activity
  2. Regulatory mutations or DNA amplification can cause over expression of receptor - hyper responsive to normal levels of growth factors
68
Q

How is the EGF receptor family an example of growth factor over expression?

A

ERBB1 - the EGF receptor - is overexpressed in 90% of epithelial head and neck tumors and over 50% of glioblastoma

69
Q

What are the basics of HER2/NEU?

A

= ERBB2
Overexpressed in 30% of breast cancers
High levels portend a poor prognosis
Treatment with antibodies (trastuzumab/herceptin) shows success

70
Q

What are the basics of RAS in tumors?

A

Most commonly mutated proto oncogene
Inactive when bound to GDP
Most common mutation is point that prevents GTP hydrolysis
Drugs interfering with signaling used clinically in chemotherapy

71
Q

How is ABL involved in tumors?

A

Non receptor associated tyrosine kinase
Proto oncogene
Translocation fuses to BCR = Philadelphia chromosome –> CML
fusion protein cannot translocation to the nucleus like usual
Imatinib/gleevec targets fusion protein - success

72
Q

In which two ways do anti growth signals prevent cell proliferation?

A

Direct division capable cells to go into G0 (quiescence)

Direct division capable cells to enter post mitotic differentiated state (senescence)

73
Q

What is the famous two hit hypothesis?

A

Inactivating mutations in both RB genes necessary for retinoblastoma tumorigenesis
Familial - kids inherit one defective and one normal RB - inheritance pattern is AD but gene acts in recessive manner

74
Q

He does RB work in the cell cycle?

A

Regulates G1 to S transition - most critical checkpoint in neoplasia
Early in G1 - active hypophosphorylated form - binds and inhibits E2F
Growth - RB hyperphosphorylated by CDKs - E2F activated and induces growth promoting cyclin E
Several viruses produce molecules that neutralize RB

75
Q

What 3 ways does p53 fight off neoplastic transformation?

A

Activation of temporary cell cycle arrest - quiescence
Induction of permanent cell cycle arrest - senescence
Triggering apoptosis

76
Q

How does p53 function upon cell stress?

A

Senses potential DNA damage and becomes free from inhibition by MDM2
Activates gene that cause cell cycle arrest to attempt to repair damage or genes that induce apoptosis if damage can’t be repaired

77
Q

What is Li-fraumeni syndrome?

A

Individuals that inherit one mutant p53 allele
Suffer from increased tumorigenesis
Normal p53 activity can be targeted by viruses

78
Q

How is the APC gene affected in APC?

A

Normally a tumor suppressor
Normally beta catenin translocation inhibited because absence of wnt signaling causes its interaction with APC which leads to degradation
Tumors - both copies of APC mutated - degradation of beta catenin no longer occurs and it constitutively translocates to nucleus and activates growth promoting cyclin d1 and Myc genes

79
Q

What are the genetics and function of APC in disease initiation?

A

APC patients generally inherit one mutant allele
Subset of polyps acquire loss of heterozygosity
Additional mutations such as RAS promote growth and progression of polyps, eventually leading to malignancy

80
Q

What is the role of BCL2 in follicular lymphomagenesis?

A

Normally anti apoptotic
Translocation causes bcl2 from chromosome 18 to go to chromosome 14 next to Ig heavy chain
High expression in follicular B cells

81
Q

How does limited replicative potential occur?

A

Most human cells can undergo 60-70 doublings in culture
Then senescence due to shortening of telomeres
Neoplastic cells can re express or overexpress telomerase to prevent telomere shortening as a cancer promoting mechanism

82
Q

How does the development of sustained angiogenesis happen?

A

Availability of oxygen becomes diffusion limited at 1-2 mm

VEGF and hif1-alpha are critical angiogenesis molecules

83
Q

What four steps are required for tumor cells to metastasize?

A

Breaking of cell cell contact
Degradation of ECM
Attachment of migrating cell to novel ECM components
Migration of tumor cells to distant sites = rate limiting step

84
Q

What is the metastatic site for cells that enter the blood supply?

A

Often first capillary bed they encounter
Liver for colon cancer
Lung for liver cancer

85
Q

What is an example of a tumor showing organ tropism?

A

Prostate adenocarcinoma show high predilection for metastasis to bone (perhaps due to hedgehog signaling)

86
Q

What are three examples of inherited mutations of genes involved in DNA repair?

A

Hereditary nonpolyposis colon cancer syndrome
Xeroderma pigmentosum
BRCA1 and BRCA2 related familial breast cancer

87
Q

What are the most common types of nonrandom structural karyotypic abnormalities in tumor cells?

A

Balanced translocations
Deletions
Gene amplifications

88
Q

What are two ways translocations typically cause tumorigenesis?

A

Overexpression of proto-oncogenes by placing under control of inappropriate promoter
Generating fusion genes

89
Q

Where are balanced translocations very common?

A

Hematopoietic neoplasms
Soft tissue sarcomas
Pediatric sarcomas - alveolar rhabdomyosarcoma and Ewing sarcoma

90
Q

How are malignant tumors in children different than in adults?

A

Sites and cells of origin are different
Often recapitulate during embryonic development
More likely to regress or mature
Better cure rate
Prognosis can vary with age
Tumor specific aberrations well recognized
Carcinomas less common, sarcomas more common

91
Q

What at common malignancies in ages 0-4 years old?

A

Neuroblastoma

Wilms tumor

92
Q

What are common malignancies in ages 5-9 years?

A

Neuroblastoma

Rhabdomyosarcoma

93
Q

What are common malignancies ages 10-14 years?

A

Osteosarcoma
Ewing sarcoma
Rhabdomyosarcoma

94
Q

Where do neuroblastoma tumors arise in children?

A

Mostly in adrenal gland
Extra adrenal tend to be paraspinous and arise from sympathetic ganglia
Over half already metastatic at presentation
Tumors produce VMA and HVA and serum or urine levels can be measured

95
Q

Where does neuroblastoma arise from?

A

Primitive neural crest cells destined to form sympathetic nervous system

96
Q

What are the characteristics of immature neuroblastomas?

A

Soft and dark reddish grey often with white foci of calcification
Contain sheets of primitive neuroblastic cells
May find rosettes of tumor cells surrounding fibrillar pink neuropil
Some neuroblasts differentiate into ganglion cells and some into Schwann cells

97
Q

What is the difference between ganglioneuroblastoma and ganglioneuroma?

A

Blastoma - tumors contain both mature and immature elements

Neuroma - only mature ganglion cells and schwannian stroma, firm and tan glistening gross appearance

98
Q

What is the prognosis of neurblastoma?

A

Infants less than a year old have better prognosis
NMYC amplification and tumor diploidy are adverse
Stage IVS - localized primary tumor associated with neuroblastic infiltrates limited to liver, skin or bone marrow - high cure rate with minimal therapy
Almost unique among malignant neoplasms due to tendency to mature or involute spontaneously or with therapy

99
Q

What is Wilms tumor?

A

Most common renal tumor of childhood
Usually presents as asymptomatic abdominal mass
Excellent prognosis
Can be sporadic or associated with genetic diseases

100
Q

How do Wilms tumors appear?

A

Large, spherical and sharply circumscribed
Soft and pale
Often contain areas of hemorrhage and necrosis
Triphasic with blastemal, epithelial and stromal components
High mitotic rate with prominent apoptosis
Most common site of metastasis is the lung

101
Q

What are the basics of rhabdomyosarcoma?

A

Most common soft tissue sarcoma of childhood
Head and neck most commonly affected followed by GI tract and pelvis and extremities
Embryonal and alveolar types
Skeletal muscle type differentiation
Immunohistochemistries are gold standard for diagnosis

102
Q

What is embryonal rhabdomyosarcoma?

A

Sheets of moderately pleomorphic and hyperchromatic small cells
Elongate or tadpole cells with dense eosinophilic cytoplasm
Tumor that arise beneath epithelial surface like bladder or vagina project into lumen like a grape and are called botryoid rhabdomyosarcoma

103
Q

What is alveolar rhabdomyosarcoma?

A

Less favorable prognosis
Translocation between FKHR on ch 13 and either PAX3 on ch 2 or PAX7 on ch1
Nests and sheets of malignant cells separated by thin fibrous septa

104
Q

What are the three categories of physical agents that can cause carcinogenesis?

A

Chemicals
Radiant energy
Microbial agents

105
Q

How does immune surveillance work?

A

Identifies tumor specific antigens

Can be tumor specific or tumor associated

106
Q

What are the two different categories of chemical carcinogens?

A

Direct acting - requir no metabolic conversion, generally weak carcinogens
Indirect acting - require metabolic conversion, stronger inducers - means that polymorphism in enzymes like p450 can have significance in dev of cancer

107
Q

What is an example of a carcinogen that can be consumed in food?

A

Aflatoxin b1 produced by strains of aspergillus that can grow on improperly stored grains and nuts

108
Q

What are the general properties of chemical carcinogens?

A

Contain reactive electrophile groups that for adducts with DNA
Oncogenes and tumor suppressor genes are imp targets
People genetically deficient for DNA repair suffer from increased risk of cancer

109
Q

What are the two types of radiation that affect carcinogenesis?

A

Ionizing - Causes chromosomal breakage and aberrations leading to genetic damage and carcinogenesis
Uv - induce formation of pyrimidine dimer within DNA leading to mutation

110
Q

What are the basics of oncogenic RNA viruses?

A

HTLV 1 is the only one shown to be directly carcinogenic
Causes a T cell leukemia
Tropism for cd4+ cells
Genome encodes TAX viral protein - activate cytokine genes and receptors in T cells causing proliferation
Starts as polyclonal but then secondary mutations lead to monoclonal leukemia

111
Q

Which DNA viruses are oncogenic?

A

EBV
HPV
hepatitis b and c

112
Q

How does EBV cause cancer?

A

Gene products contribute to oncogenesis through stimulation of B cell proliferation
Leads to secondary mutations (like MYC gene to Ig heavy chain locus)
Binds to and infects human B cells through type 2 complement receptor (cd21)

113
Q

How does HPV cause cancer?

A

Malignant forms HPV 16 and 18 produce E6 and E7 which work to cripple p53 and RB, block apoptosis
Other mutations still necessary

114
Q

How do hepatitis b and c cause cancer?

A

Dominant effect mediated by chronic inflammation, hepatocyte injury, and hepatocyte regeneration resulting in DNA damage and oncogenic gene mutations
HBV encodes HBx that activates transcription of genes encoding growth factor tgf beta and IGF-1 receptor
HCV less well understood

115
Q

What are some examples of tumor specific antigens?

A

Oncofetal antigens
Glycoproteins
Abnormal protein products of mutated protooncogenes and tumor suppressor genes
Mutated oncogenes and tumor suppressor genes
Over expressed antigens
Viral antigens

116
Q

What are some oncofetal antigens?

A

Antigens normally expressed in embryogenesis but disappear and are not normally expressed in adults
Reappear during and only during tumorigenesis
Carcinoembryonic antigen (CEA) - lesions of colon or pancreas
Alpha fetoprotein (AFP) - liver cancer and germ cell tumors, and endodermal sinus tumors (yolk sac)

117
Q

What are some glycoproteins?

A

Either excess or carb chains too long or short due to dysregulation of glycosylation
Gangliosides - normal but over expressed in melanomas and colon cancers
Mucins - may be under glycosylated - do not require MHC molecules for T cell recognition and response - in breast, pancreatic, ovarian, colonic and other carcinomas

118
Q

What are two examples of mucins?

A

CA 125 - serum marker in ovarian cancers, not specific, also in inflammatory conditions like endometriosis
CA 19-9 - sensitive, not specific, blood marker for pancreatic cancer

119
Q

How do mutated oncogenes and tumor suppressor genes act as tumor antigens?

A

Peptides from mutated forms of the proteins will only be expressed in tumor cells
May be specific for tumors in general but not for a particular cancer

120
Q

How do overexpressed antigens act as tumor antigens?

A

Not tissue specific - some on normal tissues but at low levels
Semi tumor selective

121
Q

What is the dominant anti tumor mechanism in vivo?

A

Cell mediated immunity

122
Q

What are the four types of anti tumor immune effector mechanisms?

A

Cytotoxic T cells - principally against virus associated neoplasms
Natural killer cells - IL2 activates, most active against cells with low MHC class 1
Macrophages - production of ROS or TNF
Humoral mechanisms - not against spontaneous tumors, but can derive monoclonal antibodies

123
Q

What are three ways cancers evade the immune system?

A

Selective outgrowth of antigens
Lost or reduced expression of histocompatibility molecules
Spontaneous pathogen induced and/or drug induced immunosuppression of the host

124
Q

What are the four broad kinds of tumor effects on hosts?

A

Local effects
Hormonal effects - over production of hormones native to site of tumor origin
Cancer cachexia
Paraneoplastic syndromes

125
Q

What is cancer cachexia?

A

Progressive loss of fat and muscle leading to wasting often associated with weakness or anemia
Not accounted for by metabolic requirement of tumor
Hypothesized to result from excess cytokines from tumor or through host response (TNF)

126
Q

What are paraneoplastic syndromes?

A

Syndromes not accounted for by local or distant spread of tumor
ACTH by small lung cell cancer
Inappropriate ADH in bronchogenic carcinomas
Vascular and hematologic derangements - venous thrombosis in pancreatic carcinomas

127
Q

What are three examples of hormonal effects of tumors?

A

Insulinoma of pancreas
Thyroid adenoma with thyroxin production
ACTH or prolactin producing pituitary tumors

128
Q

What are the pathology methods for lab diagnosis of cancer?

A

Histology - formalin fix and H&E stain
Cytology - individual cells on slide
Immunochemistry
Flow cytometry

129
Q

What are the two types of cytology specimens and what are advantages and disadvantages?

A

Exfoliative - removal of cells for tissue or organ (pap)
Fine needle aspiration - suck out cells from organ or mass
Advantage - quick and relatively non invasive
Disadvantages - limited specimen sample and no tissue architecture

130
Q

What is immunochemistry in lab diagnosis of cancers?

A

Use of antibody staining on tissue sections to detect presence or absence of antigens
Useful for diagnosis and prognosis
Examples - prostatic specific antigen, desmin, her2/NEU,

131
Q

What are the three applications of flow cytometry in lab diagnosis of cancers?

A

Establishment of clonality in B cell or T cell populations
Classification of hematolymphoid lineage malignancies
Analysis of nucleic acid content

132
Q

What are the four broad methods of lab diagnosis of cancer?

A

Pathology methods
Tumor markers
Molecular cancer diagnostics
Molecular profiling of tumors - gene chip technology

133
Q

What are the uses of molecular cancer diagnostics in lab diagnosis of cancers?

A

Malignancy diagnosis - flow cytometry, FISH, PCR
prognosis and behavior - her2/NEU and n-Myc in neuroblastoma
Detection of minimal residual disease - PCR can detect BCR-ABL
Diagnosis of hereditary predisposition - BRCA 1 and 2

134
Q

What is gene chip technology?

A

mRNA extracted from tumor and normal tissue of same type
Complementary DNA samples prepared and fluorescently labeled
Hybridized to a chip with cDNA proves arrayed in matrix
Laser scanner detect signals from each spot - proportional to amount of cDNA present for each gene which is proportional to original mRNA

Block 3 - Fundamentals and Heme (8 decks)

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