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Chapter 3: Neoplasia Flashcards

1
Q

What are the three main characteristics of Neoplastic growth?

A

Neoplasia is new growth that is:

  1. ) Unregulated
  2. ) Irreversible
  3. ) Monoclonal in origin
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2
Q

Historically, which enzymes isoforms are used to test for monoclonal origin of neoplastic tissue ?

A

G6PD

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3
Q

Normally, there are two isoforms of G6PD in a human cell. What occurs in women ?

A

One is inactivated via X-inactivation. This creates a mosaic effect of G6PD expression

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4
Q

Normal ratio of G6PD isoforms

A

1:1

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5
Q

What is the ratio of G6PD isoforms seen in hyperplasia ?

A

1:1. It is maintained since hyperplasia is not monoclonal

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6
Q

What marker determines the clonality of B lymphocytes ?

A

Immunglobulin Light Chain (IgL)

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7
Q

What are the two main isoforms of IgL ?

A

Kappa and Lambda

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8
Q

In normal B-cells, what is the ratio of Kappa to Lambda IgL ?

A

3:1

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9
Q

What is the ratio of Kappa to Lambda IgL in hyperplasia ?

A

3:1 (it is maintained since it is monoclonal

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10
Q

What is the ratio of Kappa to Lambda IgL in neoplasia ?

A

Kappa increased : 6:1

Lambda Increased: 3:1

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11
Q

What are the two kinds of neoplasias in terms of staging ?

A

Benign

Malignant

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12
Q

Malignant tumors have a tendency to …

A

invade locally and possibly metastasize

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13
Q

Benign tumors…

A

remain localized and do not metastasize.

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14
Q

what type of tissues form carcinoma ?

A

Epitheliod tissues

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15
Q

What type of tissues form Sarcomas ?

A

Mesenchymal

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16
Q

benign lesions typically end in which suffix ?

A

-oma

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17
Q

What are two malignancies that end in -oma ?

A

Lymphoma, Melanoma.

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18
Q

Cancer is the _____ cause of death in adults and children.

A

2nd leading

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19
Q

What is the most common cause of death in adults ?

A

Cardiovascular Disease (followed by cancer and Chronic Respiratory Disease)

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20
Q

What is the most common cause of death in children ?

A

Accidents (followed by cancer and then congenital defects)

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21
Q

What are the three most common cancers in adults ?

A
  1. Breast/Prostate
  2. Lung
  3. Colorectal
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22
Q

What are the cancers which cause the most mortality in adults ?

A
  1. Lung
  2. Breast/Prostate
  3. Colorectal
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23
Q

Starting with a single mutated cell, how many divisions occur before the earliest signs of cancer occur ?

A

30

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24
Q

What is the goal of screening ?

A
  1. Finding dysplasia before it turns to neoplasia

2. Finding neoplasias that may turn malignant.

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25
Q

What does a Pap Smear detect ?

A

Cervical dysplasia

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26
Q

What does mammography detect ?

A

in situ breast cancer (has gone through the basement membrane but not to local lymph nodes)

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27
Q

PSA and Digital Rectal Exams detect ?

A

Prostate Carcinoma (usually clinically silent since it does not press on the urethra until late stage)

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28
Q

Hematocult test detects ?

A

Colonic carcinoma

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29
Q

What are the three major forms of Carcinogens ?

A

Chemical
Viral
Radiation

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30
Q

Protooncogenes are normal genes which stimulate…

A

Growth and differentiation

When mutated they lead to unregulated growth and differentiation. (usually some form of gain of function)

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31
Q

What are the 5 Major Classes of Proto-oncogenes ?

A 
Growth Factors 
Growth Factor Receptors
SIgnal Transducers 
Nuclear Regulators
Cell Cycle Regulators
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32
Q

What is an important examples of Growth Factor proto-oncogenes ?

A

PDGFB (Platelet Derived Growth Factor Beta)

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33
Q

What tumor is associated with PDGFB ?

A

Astrocytoma

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34
Q

What mechanism occurs in PDGFB mutation that leads to neoplasia ?

A

Overexpression (Of PDGFB)

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35
Q

Which Growth Factor Receptor is mutated and associated with Breast Carcinoma ?

A

HER2/neu (Epithelial GFR)

aka Estrogen Receptor BB2 (ERBB2)

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36
Q

What mechanism occurs in HER2/neu mutation that leads to neoplasia ?

A

Amplification

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37
Q

When the Growth Factor Receptor RET undergoes POINT MUTATION, what tumor occurs ?

A

Medullary Thyroid Carcinoma (MTC)

Associated with:
MEN2A (MTC, Parathyroid hyperplasia, pheo.)
MEN2B (MTC, submucosal neoplasm, pheo)

RET (Neuronal GFR)

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38
Q

Gastrointestinal Stromal Tumors are associated with POINT MUTATION in which Growth Factor Receptor ?

A

KIT

Stem Cell GFR

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39
Q

Mutations in this Signal Transducer is seen in 70-80% of all cancers (carcinoma, melanoma, lymphoma) ?

A

RAS

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40
Q

What kind of mutations in RAS lead to neoplasm ?

A

Point Mutations

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41
Q

What kind of molecule is RAS associated with in its active state ?

A

GTP

RAS is a GTP binding protein (GDP bound = inactive)
Mutation often causes an inability to hydrolyze GTP to GDP

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42
Q

ABL is a signal transducer that is associated with which translocation seen in CML and Adult ALL ?

A

9:22 (Philadelphia Chromosome)

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43
Q

ABL is turned on by what kind of receptor complex ?

A

Tyrosine Kinase

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44
Q

In Burkitt Lymphoma, what translocation is responsible for a amplification of c-Myc ?

A

8:14

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45
Q

c-Myc is what kind of molecule ?

A

Nuclear Regulator (Transcription Factor)

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46
Q

Amplification fo N-myc (a transcription factor) leads to the formation of what cancer ?

A

Neuroblastoma

N= neuroblastoma

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47
Q

Amplification of L-Myc (a transcription factor) leads to the formation of what cancer ?

A

Small Cell LUNG carcinoma

L for Lung

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48
Q

Mantle Cell Lymphoma is caused by what translocation ?

A

11:14

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49
Q

What protooncogene is amplified in Mantle Cell Lymphoma due to the 11:14 translocation ?

A

Cyclin D (Cell Cycle Regulator)

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50
Q

Melanoma is associated with amplification of which Cell Cycle Regulator ?

A

Cyclin Dependent Kinase IV (CDK4)

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51
Q

What is found on chromosome 14 that allows for the amplification of c-Myc (Burkitts Lymphoma, 8:14) and cyclin D (Mantle Cell Lymphoma, 11:14) ?

A

The locus for the promoter of Immunoglobulin Heavy Chain

Burkitts and Mantle Cell are both B-Cell diseases. B-cells produce a lot of Ig. When the gene for c-Myc or Cyclin D are placed next to this promoter, their production is increased !

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52
Q

Aflatoxins are derived from which yeast ?

A

Aspergillus (seen on contaminated rice and grains)

53
Q

What cancer is associated with aflatoxin exposure

A

Hepatocellular Carcinoma

54
Q

Alkylating agents are common chemotherapeutic agents. They are also associated with which post treatment cancer ?

A

Leukemia and Lymphoma

55
Q

Alcohol is associated with Carcinoma of…

A

Oropharynx and Upper Esophagus (SquamousCell)

Hepatocellular Carcinoma

56
Q

Arsenic is a common component of what other carcinogen ?

A

Cigarette smoke

57
Q

Arsenic causes squamous cell carcinoma of the ________ and Angiosacroma of the _________

A

SCC: Skin, Lung
Angiosarcoma: Liver

58
Q

Asbestos causes which two cancers ?

A

Lung Carcinoma

Mesothelioma

59
Q

Which is more prevalent in asbestos exposure: Lung Cancer of Mesothelioma ?

A

Lung Carcinoma !

Asbestos is more associated though.

60
Q

On top of causing carcinoma of the oropharynx, esophagus and lung, Cigarette Smoke causes carcinoma of which other three organs ?

A

Kidney
Bladder
Pancreas

61
Q

What is the major carcinogen associated with cigarette smoke ?

A

polycyclic hydrocarbons.

62
Q

Nitrosamines are mostly associated with which cancer ?

A

Stomach Carcinoma

63
Q

What are common sources of nitrosamines ?

A

Smoked foods

64
Q

This carcinogen is found in cigarette smoke and is responsible for urothelial carcinoma of the bladder…

A

Napthylamine

65
Q

Vinyl Chloride is associated with what kind of liver cancer ?

A

Angiosarcoma of the Liver.

Think PVC Pipes

66
Q

Nickel, Chromium, Berrylium and SILICA* are associated with what kind of cancer ?

A

Lung Carcinoma

67
Q

Epstein Barr Virus is associates with three cancers. List them :

A

Nasopharyngeal Carcinoma
Burkitts Lymphoma
CNS Lymphoma

68
Q

Who is at risk for Nasopharyngeal Carcinoma when infected with EBV ?

A

Chinese Men

69
Q

Who is at risk for Burkitt Lymphoma when infected with EBV ?

70
Q

Who is at risk for CNS lymphoma when infected with EBV ?

A

AIDS patients

71
Q

Kaposi Sarcoma is associated with which virus ?

72
Q

What three groups do you typically see Kaposi Sarcoma in ?

A

Eastern European (Or mediteranean)
AIDS Patients
Transplant Recipients

73
Q

HBV and HCV cause what kind of cancer

A

Hepatocellular Carcinoma

74
Q

Adult T-Cell Leukemia/Lymphoma is caused by what virus ?

75
Q

Human Papilloma Virus cause increased risk of Squamous Cell Carcinoma in which tissues ?

A

vulva, vagina, anus and cervix

May also see adenocarcinoma in Cervix

76
Q

Ionizing radiation is associated with which cancers ?

A

AML, CML and Papillary Carcinoma of Thyroid

77
Q

How does ionizing radiation lead to tumorigenesis ?

A

Causes Hydroxyl Free Radicals

78
Q

Non-Ionizing Radiation is associated with ….

A

Basal cell carcinoma, SCC and melanoma of the Skin

79
Q

How does Non-ionizing Radiation cause tumorigenesis ?

A

Formation of pyrimidine dimers that are not properly excised by restriction endonucleases.

80
Q

p53 and Rb are both Tumor Suppressor genes and regulate the progression of the cell cycle between which two phases ?

81
Q

If there is DNA damage to a cell, p53 will either slow down the cycle so that the DNA can be fixed or it will signal for what action in the cell ?

82
Q

What protein does p53 activate that will help in initiation of apoptosis ?

83
Q

What protein does Bax inhibit to initiate apoptosis ?

84
Q

What is the role of Bcl-2 ?

A

Stabilizes the mitochondrial membrane

85
Q

What occurs when Bcl-2 is inhibited by Bax ?

A

Cytochrome C will leak out of the mitochondria and activate capspases that will cause apoptosis .

86
Q

What will occur if p53 is mutated ?

A

loss of function, decreased ability to signal for apoptosis in cells.

87
Q

Will one mutated gene of p53 be sufficient to elicit tumorigenesis ?

A

No, you need two ! One good copy is still capable of sustaining Tumor Suppressor Capability

88
Q

Rb also regulates G1–>S phase transition in cells. What transcription factor is Rb in charge of sequestering ?

89
Q

Rb releases E2F upon phosphorylization. What leads to phosphorlyization of Rb ?

A

CyclinD/ CDK4 complex

Review: What is associated with Cyclin D and CDK4 amplification ? Mantle Cell Lymphoma (11:14) and Melanoma … Respectively.

90
Q

What is the roll of E2F ?

A

Critical transcription factor in G1–>S Transition

91
Q

What does Rb mutation lead to ?

A

Inability to hold E2F –> uncontrolled growth of cells

92
Q

Describe the etiology and distribution of Sporadic Retinoblastoma :

A

Etiology: 2 somatic mutations (not germline)
Distribution: Unilateral (only seen in one eye)

93
Q

Describe the etiology and distribution of Familial Retinoblastoma :

A

Etiology: One hit is germ line, the other is somatic
Distribution: Bilateral retinoblastoma and osteosarcoma.

94
Q

Bcl-2 is a regulator of apoptosis which stabilizes the mitochondrial membrane. Bcl-2 is over expressed in which disease ?

A

Follicular Lymphoma

95
Q

What translocation is associated with Follicular Lymphoma and bcl-2 over expression ?

96
Q

Again, what is found on chromosome 14 that allows for over expression of bcl-2 ?

A

Immunoglobulin Heavy Chain Promoter.

Follicular Lymphoma is a B-cell disease ( lots of IgH , if bcd-2 is placed nearby, you will get over expression of it)

97
Q

What occurs to telomeres as cells senesce ?

A

It shortens

98
Q

What enzyme is used to immortalize tumor cells by regulating telomeres ?

A

Telomerase

99
Q

What two angiogenic molecules are commonly produced by tumor cells ?

A

FGF and VEGF

100
Q

What molecule is sensed by Cytotoxic T cells and is down regulated in cancer cells to avoid immunosurveilance ?

A

MHC-1

Still NK cells sense the lack of MCH1 and kill cells

101
Q

Epithelial cells are typically held together by CAM’s. What particular CAM is down regulated in many cancers leading to dissociation of epitheliod tumors and allowing for spread?

A

E-cadherin.

102
Q

Entrance into which two spaces allows for metastases of tumor cells ?

A

Vascular and Lymphatic

103
Q

After attaching to Lamnin in the basement membrane, tumor cells can escape by destroying what molecule ?

A

Collagen IV (using collagenase)

104
Q

lymphatic spread is characteristic of …

A

Carcinoma (with 4 exceptions)

105
Q

Hematogenous spread is indicative of …

A

Sarcoma (except the 4 carcinomas that do )

106
Q

Wht are the 4 carcinomas that spread hematogenously ?

A

Renal Carcinoma (Renal vein)
Hepatocellular Carcinoma
Follicular Cell Carcinoma (Thyroid)
Chroriocarcinoma

107
Q

Slow growing, well circumscribed, mobile and distinct

A

benign tumor

108
Q

rapidly growing, poorly circumscribed , infiltrative and transfixed to tissue

A

Malignant Tumor

109
Q

What is necessary before a tumor can be classified benign or malignant ?

110
Q

Uniform Nuclei, Low Nucleus:Cytoplasm, Lack invasions and no Metastatic potential

111
Q

Disorganized growth, High Nuclear:Cytoplasm, High mitotic activity, Invasion

A

Malignanat

112
Q

benign tumors NEVER….

A

metastasize

113
Q

Immunohistochemistry is useful in determining …

A

tumor tissue of origin

114
Q

Immunohistochemisty showing keratin is indicative of …

A

epithelial origin

115
Q

Immunohistochemisty showing Vimentin is indicative of …

A

mesenchymal origin

116
Q

Immunohistochemisty showing Desmin is indicative of …

A

Muscular origin (Rhabdomyo or Leiomyo)

117
Q

Immunohistochemisty showing GFAP is indicative of …

A

Neuroglial origin

118
Q

Immunohistochemisty showing Neurofilament is indicative of …

A

Neuronal origin

119
Q

Immunohistochemisty showing PSA is indicative of …

A

Prostatic Epithelial Origina

120
Q

Immunohistochemisty showing Estrogen Receptors is indicative of …

A

Breast Epithelium

121
Q

Immunohistochemisty showing Thyroglobulin is indicative of …

A

Thyroid Follicular Cells

122
Q

Immunohistochemisty showing CHROMAGRANIN is indicative of … (KNOW THIS !)

A

Neuroendocrine origin (Small Cell Carcinoma or Lung and Carcinoid Tumor)

123
Q

Immunohistochemisty showing S-100 is indicative of …

A

Melanoma
Schwannoma
Langerhancell Histiocytosis

124
Q

are serum tumor makers diagnostic ?

A

NO ! they are for screening. Diagnosis requires biopsy

125
Q

Grading mainly entails…

A

assessment of differentiation (how much a tumor resembles parent tissue)

126
Q

High Grade :

A

does not resemble parent (poorly differentiated)

127
Q

Low Grade:

A

looks a lot like the parent

Well differentiated

128
Q

What is more important: Grading or Staging ?

A

Staging !!!!!!!!!!! Key Prognostic Factor

129
Q

What are the three parts of tumor staging ?

A

TNM
T: Tumor Size
N:Spread to lymph nodes
M:Metastases (MOST IMPORTANT PROGNOSTIC FACTOR)

Pathoma (15 decks)

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