Chapter 3: Neoplasia Flashcards
1
Q
What are the three main characteristics of Neoplastic growth?
A
Neoplasia is new growth that is:
- ) Unregulated
- ) Irreversible
- ) Monoclonal in origin
2
Q
Historically, which enzymes isoforms are used to test for monoclonal origin of neoplastic tissue ?
A
G6PD
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
4
Q
Normal ratio of G6PD isoforms
A
1:1
5
Q
What is the ratio of G6PD isoforms seen in hyperplasia ?
A
1:1. It is maintained since hyperplasia is not monoclonal
6
Q
What marker determines the clonality of B lymphocytes ?
A
Immunglobulin Light Chain (IgL)
7
Q
What are the two main isoforms of IgL ?
A
Kappa and Lambda
8
Q
In normal B-cells, what is the ratio of Kappa to Lambda IgL ?
A
3:1
9
Q
What is the ratio of Kappa to Lambda IgL in hyperplasia ?
A
3:1 (it is maintained since it is monoclonal
10
Q
What is the ratio of Kappa to Lambda IgL in neoplasia ?
A
Kappa increased : 6:1
Lambda Increased: 3:1
11
Q
What are the two kinds of neoplasias in terms of staging ?
A
Benign
Malignant
12
Q
Malignant tumors have a tendency to …
A
invade locally and possibly metastasize
13
Q
Benign tumors…
A
remain localized and do not metastasize.
14
Q
what type of tissues form carcinoma ?
A
Epitheliod tissues
15
Q
What type of tissues form Sarcomas ?
A
Mesenchymal
16
Q
benign lesions typically end in which suffix ?
A
-oma
17
Q
What are two malignancies that end in -oma ?
A
Lymphoma, Melanoma.
18
Q
Cancer is the _____ cause of death in adults and children.
A
2nd leading
19
Q
What is the most common cause of death in adults ?
A
Cardiovascular Disease (followed by cancer and Chronic Respiratory Disease)
20
Q
What is the most common cause of death in children ?
A
Accidents (followed by cancer and then congenital defects)
21
Q
What are the three most common cancers in adults ?
A
- Breast/Prostate
- Lung
- Colorectal
22
Q
What are the cancers which cause the most mortality in adults ?
A
- Lung
- Breast/Prostate
- Colorectal
23
Q
Starting with a single mutated cell, how many divisions occur before the earliest signs of cancer occur ?
A
30
24
Q
What is the goal of screening ?
A
- Finding dysplasia before it turns to neoplasia
2. Finding neoplasias that may turn malignant.
25
What does a Pap Smear detect ?
Cervical dysplasia
26
What does mammography detect ?
in situ breast cancer (has gone through the basement membrane but not to local lymph nodes)
27
PSA and Digital Rectal Exams detect ?
Prostate Carcinoma (usually clinically silent since it does not press on the urethra until late stage)
28
Hematocult test detects ?
Colonic carcinoma
29
What are the three major forms of Carcinogens ?
Chemical
Viral
Radiation
30
Protooncogenes are normal genes which stimulate...
Growth and differentiation
| When mutated they lead to unregulated growth and differentiation. (usually some form of gain of function)
31
What are the 5 Major Classes of Proto-oncogenes ?
```
Growth Factors
Growth Factor Receptors
SIgnal Transducers
Nuclear Regulators
Cell Cycle Regulators
```
32
What is an important examples of Growth Factor proto-oncogenes ?
PDGFB (Platelet Derived Growth Factor Beta)
33
What tumor is associated with PDGFB ?
Astrocytoma
34
What mechanism occurs in PDGFB mutation that leads to neoplasia ?
Overexpression (Of PDGFB)
35
Which Growth Factor Receptor is mutated and associated with Breast Carcinoma ?
HER2/neu (Epithelial GFR)
| aka Estrogen Receptor BB2 (ERBB2)
36
What mechanism occurs in HER2/neu mutation that leads to neoplasia ?
Amplification
37
When the Growth Factor Receptor RET undergoes POINT MUTATION, what tumor occurs ?
Medullary Thyroid Carcinoma (MTC)
Associated with:
MEN2A (MTC, Parathyroid hyperplasia, pheo.)
MEN2B (MTC, submucosal neoplasm, pheo)
RET (Neuronal GFR)
38
Gastrointestinal Stromal Tumors are associated with POINT MUTATION in which Growth Factor Receptor ?
KIT
| Stem Cell GFR
39
Mutations in this Signal Transducer is seen in 70-80% of all cancers (carcinoma, melanoma, lymphoma) ?
RAS
40
What kind of mutations in RAS lead to neoplasm ?
Point Mutations
41
What kind of molecule is RAS associated with in its active state ?
GTP
RAS is a GTP binding protein (GDP bound = inactive)
Mutation often causes an inability to hydrolyze GTP to GDP
42
ABL is a signal transducer that is associated with which translocation seen in CML and Adult ALL ?
9:22 (Philadelphia Chromosome)
43
ABL is turned on by what kind of receptor complex ?
Tyrosine Kinase
44
In Burkitt Lymphoma, what translocation is responsible for a amplification of c-Myc ?
8:14
45
c-Myc is what kind of molecule ?
Nuclear Regulator (Transcription Factor)
46
Amplification fo N-myc (a transcription factor) leads to the formation of what cancer ?
Neuroblastoma
| N= neuroblastoma
47
Amplification of L-Myc (a transcription factor) leads to the formation of what cancer ?
Small Cell LUNG carcinoma
| L for Lung
48
Mantle Cell Lymphoma is caused by what translocation ?
11:14
49
What protooncogene is amplified in Mantle Cell Lymphoma due to the 11:14 translocation ?
Cyclin D (Cell Cycle Regulator)
50
Melanoma is associated with amplification of which Cell Cycle Regulator ?
Cyclin Dependent Kinase IV (CDK4)
51
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) ?
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 !
52
Aflatoxins are derived from which yeast ?
Aspergillus (seen on contaminated rice and grains)
53
What cancer is associated with aflatoxin exposure
Hepatocellular Carcinoma
54
Alkylating agents are common chemotherapeutic agents. They are also associated with which post treatment cancer ?
Leukemia and Lymphoma
55
Alcohol is associated with Carcinoma of...
Oropharynx and Upper Esophagus (SquamousCell)
Hepatocellular Carcinoma
56
Arsenic is a common component of what other carcinogen ?
Cigarette smoke
57
Arsenic causes squamous cell carcinoma of the ________ and Angiosacroma of the _________
SCC: Skin, Lung
Angiosarcoma: Liver
58
Asbestos causes which two cancers ?
Lung Carcinoma
| Mesothelioma
59
Which is more prevalent in asbestos exposure: Lung Cancer of Mesothelioma ?
Lung Carcinoma !
| Asbestos is more associated though.
60
On top of causing carcinoma of the oropharynx, esophagus and lung, Cigarette Smoke causes carcinoma of which other three organs ?
Kidney
Bladder
Pancreas
61
What is the major carcinogen associated with cigarette smoke ?
polycyclic hydrocarbons.
62
Nitrosamines are mostly associated with which cancer ?
Stomach Carcinoma
63
What are common sources of nitrosamines ?
Smoked foods
64
This carcinogen is found in cigarette smoke and is responsible for urothelial carcinoma of the bladder...
Napthylamine
65
Vinyl Chloride is associated with what kind of liver cancer ?
Angiosarcoma of the Liver.
Think PVC Pipes
66
Nickel, Chromium, Berrylium and SILICA* are associated with what kind of cancer ?
Lung Carcinoma
67
Epstein Barr Virus is associates with three cancers. List them :
Nasopharyngeal Carcinoma
Burkitts Lymphoma
CNS Lymphoma
68
Who is at risk for Nasopharyngeal Carcinoma when infected with EBV ?
Chinese Men
69
Who is at risk for Burkitt Lymphoma when infected with EBV ?
Africans
70
Who is at risk for CNS lymphoma when infected with EBV ?
AIDS patients
71
Kaposi Sarcoma is associated with which virus ?
HHV-8
72
What three groups do you typically see Kaposi Sarcoma in ?
Eastern European (Or mediteranean)
AIDS Patients
Transplant Recipients
73
HBV and HCV cause what kind of cancer
Hepatocellular Carcinoma
74
Adult T-Cell Leukemia/Lymphoma is caused by what virus ?
HTLV-1
75
Human Papilloma Virus cause increased risk of Squamous Cell Carcinoma in which tissues ?
vulva, vagina, anus and cervix
May also see adenocarcinoma in Cervix
76
Ionizing radiation is associated with which cancers ?
AML, CML and Papillary Carcinoma of Thyroid
77
How does ionizing radiation lead to tumorigenesis ?
Causes Hydroxyl Free Radicals
78
Non-Ionizing Radiation is associated with ....
Basal cell carcinoma, SCC and melanoma of the Skin
79
How does Non-ionizing Radiation cause tumorigenesis ?
Formation of pyrimidine dimers that are not properly excised by restriction endonucleases.
80
p53 and Rb are both Tumor Suppressor genes and regulate the progression of the cell cycle between which two phases ?
G1--> S
81
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 ?
Apoptosis
82
What protein does p53 activate that will help in initiation of apoptosis ?
Bax
83
What protein does Bax inhibit to initiate apoptosis ?
Bcl-2
84
What is the role of Bcl-2 ?
Stabilizes the mitochondrial membrane
85
What occurs when Bcl-2 is inhibited by Bax ?
Cytochrome C will leak out of the mitochondria and activate capspases that will cause apoptosis .
86
What will occur if p53 is mutated ?
loss of function, decreased ability to signal for apoptosis in cells.
87
Will one mutated gene of p53 be sufficient to elicit tumorigenesis ?
No, you need two ! One good copy is still capable of sustaining Tumor Suppressor Capability
88
Rb also regulates G1-->S phase transition in cells. What transcription factor is Rb in charge of sequestering ?
E2F
89
Rb releases E2F upon phosphorylization. What leads to phosphorlyization of Rb ?
CyclinD/ CDK4 complex
Review: What is associated with Cyclin D and CDK4 amplification ? Mantle Cell Lymphoma (11:14) and Melanoma ... Respectively.
90
What is the roll of E2F ?
Critical transcription factor in G1-->S Transition
91
What does Rb mutation lead to ?
Inability to hold E2F --> uncontrolled growth of cells
92
Describe the etiology and distribution of Sporadic Retinoblastoma :
Etiology: 2 somatic mutations (not germline)
Distribution: Unilateral (only seen in one eye)
93
Describe the etiology and distribution of Familial Retinoblastoma :
Etiology: One hit is germ line, the other is somatic
Distribution: Bilateral retinoblastoma and osteosarcoma.
94
Bcl-2 is a regulator of apoptosis which stabilizes the mitochondrial membrane. Bcl-2 is over expressed in which disease ?
Follicular Lymphoma
95
What translocation is associated with Follicular Lymphoma and bcl-2 over expression ?
14:18
96
Again, what is found on chromosome 14 that allows for over expression of bcl-2 ?
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
What occurs to telomeres as cells senesce ?
It shortens
98
What enzyme is used to immortalize tumor cells by regulating telomeres ?
Telomerase
99
What two angiogenic molecules are commonly produced by tumor cells ?
FGF and VEGF
100
What molecule is sensed by Cytotoxic T cells and is down regulated in cancer cells to avoid immunosurveilance ?
MHC-1
| Still NK cells sense the lack of MCH1 and kill cells
101
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?
E-cadherin.
102
Entrance into which two spaces allows for metastases of tumor cells ?
Vascular and Lymphatic
103
After attaching to Lamnin in the basement membrane, tumor cells can escape by destroying what molecule ?
Collagen IV (using collagenase)
104
lymphatic spread is characteristic of ...
Carcinoma (with 4 exceptions)
105
Hematogenous spread is indicative of ...
Sarcoma (except the 4 carcinomas that do )
106
Wht are the 4 carcinomas that spread hematogenously ?
Renal Carcinoma (Renal vein)
Hepatocellular Carcinoma
Follicular Cell Carcinoma (Thyroid)
Chroriocarcinoma
107
Slow growing, well circumscribed, mobile and distinct
benign tumor
108
rapidly growing, poorly circumscribed , infiltrative and transfixed to tissue
Malignant Tumor
109
What is necessary before a tumor can be classified benign or malignant ?
BIOPSY !
110
Uniform Nuclei, Low Nucleus:Cytoplasm, Lack invasions and no Metastatic potential
Benign
111
Disorganized growth, High Nuclear:Cytoplasm, High mitotic activity, Invasion
Malignanat
112
benign tumors NEVER....
metastasize
113
Immunohistochemistry is useful in determining ...
tumor tissue of origin
114
Immunohistochemisty showing keratin is indicative of ...
epithelial origin
115
Immunohistochemisty showing Vimentin is indicative of ...
mesenchymal origin
116
Immunohistochemisty showing Desmin is indicative of ...
Muscular origin (Rhabdomyo or Leiomyo)
117
Immunohistochemisty showing GFAP is indicative of ...
Neuroglial origin
118
Immunohistochemisty showing Neurofilament is indicative of ...
Neuronal origin
119
Immunohistochemisty showing PSA is indicative of ...
Prostatic Epithelial Origina
120
Immunohistochemisty showing Estrogen Receptors is indicative of ...
Breast Epithelium
121
Immunohistochemisty showing Thyroglobulin is indicative of ...
Thyroid Follicular Cells
122
Immunohistochemisty showing CHROMAGRANIN is indicative of ... (KNOW THIS !)
Neuroendocrine origin (Small Cell Carcinoma or Lung and Carcinoid Tumor)
123
Immunohistochemisty showing S-100 is indicative of ...
Melanoma
Schwannoma
Langerhancell Histiocytosis
124
are serum tumor makers diagnostic ?
NO ! they are for screening. Diagnosis requires biopsy
125
Grading mainly entails...
assessment of differentiation (how much a tumor resembles parent tissue)
126
High Grade :
does not resemble parent (poorly differentiated)
127
Low Grade:
looks a lot like the parent
| Well differentiated
128
What is more important: Grading or Staging ?
Staging !!!!!!!!!!! Key Prognostic Factor
129
What are the three parts of tumor staging ?
TNM
T: Tumor Size
N:Spread to lymph nodes
M:Metastases (MOST IMPORTANT PROGNOSTIC FACTOR)
