Pathoma Chapter 3D

Question 1

Knudson two-hit hypothesis

Answer 1

both copies of the p53 gene must be knocked out for tumor formation, Both copies of Rb gene must be knocked out for tumor formation

Question 2

Loss of p53 is seen in what percentage of cancers?

Answer 2

>50% of cancers.

Question 3

p53 Germline mutation results in

Answer 3

Li-Fraumeni syndrome (2nd hit is somatic),

Question 4

Li-Fraumeni syndrome is characterized by?

Answer 4

the propensity to develop multiple types of carcinomas and sarcomas,

Question 5

Rb

Answer 5

regulates progression from G0 to S phase.

Question 6

How does Rb regulate the progression to S phase?

Answer 6

holds the E2F transcription factor, which is necessary for transition to the S phase

Question 7

E2F is released when?

Answer 7

RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex

Question 8

Rb mutation results in

Answer 8

constitutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells.

Question 9

Sporadic mutation

Answer 9

(both hits are somatic) and it is characterized by unilateral retinoblastoma

Question 10

Rb Germline mutation results in

Answer 10

familial retinoblastoma (2nd hit is somatic) and is characterized by bilateral retinoblastoma and osteosarcoma.

Question 11

What is the function of regulators of apoptosis?

Answer 11

Prevent apoptosis in normal cells, but promote apoptosis in mutated cells whose DNA cannot be repaired (e.g Bcl2)

Question 12

Bcl2

Answer 12

normally stabilizes the mitochondrial membrane, blocking release of cytochrome c

Question 13

Disruption of Bcl2 allows what to happen?

Answer 13

Cytochrome c to leave the mitochondria and activate apoptosis

Question 14

Bcl2 in follicular lymphoma?

Answer 14

it is overexpressed in follicular lymphoma,

Question 15

Why is Bcl2 overexpressed in follicular lymphoma?

Answer 15

t(14;18) moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chromosome 14), resulting in increased Bcl2.

Question 16

How is apoptosis inhibited in follicular lymphoma?

Answer 16

Mitochondrial membrane is further stabilized by overexpressed Bcl2, prohibiting apoptosis.

Question 17

In follicular lymphoma, how does the inhibition of apoptosis lead to lymphoma?

Answer 17

B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma.

Question 18

What is necessary for cell immortality?

Answer 18

Telomerase

Question 19

Normally telomeres do what?

Answer 19

shorten with serial cell divisions, eventually resulting in cellular senescence

Question 20

What is the relationship between cancers and telomerase?

Answer 20

cancers often have up regulated telomerase, which preserves telomeres

Question 21

Angiogenesis and tumors

Answer 21

(production of new blood vessels) is necessary for tumor survival and growth.

Question 22

FGF and VEGF

Answer 22

(angiogenic factors) are commonly produced by tumor cells.

Question 23

Tumor survival and the immune system?

Answer 23

Avoiding immune surveillance is necessary for tumor survival

Question 24

Immune surveillance and tumor survival?

Answer 24

Mutations often result in production of abnormal proteins, which are expressed on MHC class 1, CD8+ T cells detect and destroy such mutated cells, Tumor cells can evade immune surveillance by downregulating expression of MHC class 1.

Question 25

How do tumor cells evade immune surveillance?

Answer 25

by downregulating MHC class 1

Question 26

Immunodeficiency and cancer

Answer 26

(both primary and secondary) increases risk for cancer

Question 27

Accumulation of mutations eventually result in what?

Answer 27

tumor invasion and spread

Question 28

Epithelial tumor cells are normally attached to one another by what?

Answer 28

cellular adhesion molecules (e.g., E-cadherin).

Question 29

Downregulalion of E-cadherin leads to what?

Answer 29

dissociation of attached cells

Question 30

How do the tumor cells spread locally?

Answer 30

Cells attach to laminin and destroy basement membrane (collagen type IV) via collagenase. Cells attach to fibronectin in the extracellular matrix and spread locally

Question 31

Metastasis of tumor cells.

Answer 31

Entrance into vascular or lymphatic spaces allows for metastasis (distant spread)

Question 32

What are the routes of metastasis?

Answer 32

Lymphatic, hematogenous, seeding of body cavities

Question 33

Lymphatic spread is characteristic of what?

Answer 33

carcinomas

Question 34

Where does the initial lymphatic spread occur?

Answer 34

In the regional draining lymph nodes

Question 35

Hematogenous spread is characteristic of what?

Answer 35

sarcomas and some carcinomas

Question 36

What are some examples of hematogenous spread?

Answer 36

renal cell carcinoma, hepatocellular carcinoma, follicular carcimoma of the thyroid, choriocarcinoma

Question 37

Seeding of body cavities is characteristic of?

Answer 37

ovarian carcinoma, often involves the peritoneum ‘omental caking’

Question 38

What is omental caking?

Answer 38

where the peritoneum is often involved in ovarian carcinoma

Question 39

Describe benign tumors.

Answer 39

tend to be slow growing, well circumscribed, distinct, and mobile

Question 40

Malignant tumors are usually

Answer 40

rapid growing, poorly circumscribed, infiltrative, and fixed to surrounding tissues and local structures.

Question 41

What is generally required before a tumor can be classified as benign or malignant with certainty?

Answer 41

Biopsy or excision

Question 42

Why is biopsy necessary?

Answer 42

Some benign tumors can grow in a malignant-like fashion, and some malignant tumors can grow in a benign-like fashion.

Question 43

Benign tumors are usually

Answer 43

well differentiated

Question 44

What are some characteristics of benign tumors?

Answer 44

1. Organized growth 2. Uniform nuclei 3. Low nuclear to cytoplasmic ratio 4. Minimal mitotic activity 5. Lack of invasion (of basement membrane or local tissue) 6. No metastatic potential