Ch 3 Principles of Neoplasia

Question 1

Characteristics of neoplasia (3)

Answer 1

unregulated, irreversible, monoclonal

Question 2

Explain how clonality of B lymphocytes are determined

Answer 2

1. Ig requires heavy chain and light chain
2. Light chain uses kappa and lambda, which is usually 3:1
3. Hyperplasia will maintain 3:1 ratio, but neoplasia will be 6:1 or 1:3 kappa/lambda, because all are monoclonal

Question 3

mechanism of tumor progression and spread (4)

Answer 3

1. downregulation of e-cadherin, disassociation of attached cells
2. attaches to laminin and destroys basement membrane using collagenase
3. attaches to fibronectin
4. gains access to either lymphatics or blood vessels

Question 4

What is mantle cell lymphoma and why does it happen

Answer 4

LN: follicle, mantle, margin. t(11;14) Cyclin D1 locus gets moved to IgH locus

Question 5

Aflatoxins

Answer 5

HCC; derived from aspergillus, stored grains

Question 6

HBV and HCV

Answer 6

DNA and RNA virus respectively- HCC

Question 7

Cigarette smoke

Answer 7

oropharynx, esophagus, lung, kidney, bladder, pancreas; most common carcinogen in the world, polycyclic hydrocarbons worst, urothelium marinade

Question 8

EBV

Answer 8

NPC, burkitt lymphoma, CNS lymphoma in AIDS

Question 9

Carcinogens (3)

Answer 9

chemicals, oncogenic viruses, radiation (io and non-ionizing)

Question 10

Grading of CA

Answer 10

well differentiated (low grade)- resembles normal parent tissue, poorly differentiated (high grade)- does not resemble parent tissue

Question 11

Nickel, chromium, berrylium or silica

Answer 11

Lung CA, occupational exposure

Question 12

Alkylating agents

Answer 12

lymphoma/leukemia; side effect of chemo

Question 13

ERBB2 (HER2/neu)

Answer 13

GF-R, uses amplification, some breast carcinomas

Question 14

HHV-8 (def, 3 ppl groups and treatment for each)

Answer 14

Kaposi sarcoma (tumor of endothelial cells); 1. Eastern europeans (excise) 2. AIDS (retroviral) 3. Transplanted (lower dose of immunosuppresants)

Question 15

progression of oncogenes

Answer 15

1. growth factor induces signal
2. growth factor receptor mediate signal
3. signal transducers relay receptor activation to nucleus
4. cell-cycle regulators mediate progression through cell cycle

Question 16

Role of cancer screening (1)

Answer 16

catch dysplasia before cancer, catch cancer before symptoms arise (average of 30 mutations)

Question 17

GFAP (IHC)

Answer 17

neuroglia

Question 18

KIT

Answer 18

GF-R, a/w gastrointestinal stromal tumor (GIST)

Question 19

Naphthylamine

Answer 19

Urothelial CA of bladder; from smoking

Question 20

HTLV-1

Answer 20

Adult T-cell leukemia/lymphoma

Question 21

cyclin D-1

Answer 21

cell cycle regulator; cyclin with t(11;14) involving IgH, a/w mantle cell lymphoma

Question 22

l-MHC

Answer 22

TF, a/w small cell carcinoma of lung

Question 23

follicular lymphoma mechanism

Answer 23

1. t(14;18) moves Bcl2 locus to IgH locus (on chromosome 14)
2. Increased Bcl2 production
3. Mitochondrial membrane stabilized, prohibiting apoptosis
4. B-cells that should undergo apoptosis during somatic hypermutation in LN germinal center accumulate = lymphoma

Question 24

Key regulatory systems that allow for tumor growth and progression (3)

Answer 24

oncogenes, tumor suppressors, regulators of apoptosis

Question 25

HPV

Answer 25

SCC of vulva, vagina, anus, cervix, adenoCA of cervix

Question 26

desmin (IHC)

Answer 26

muscle

Question 27

Nitrosamines

Answer 27

Stomach CA, smoked foods in Japan

Question 28

vimentin (IHC)

Answer 28

mesenchyme muscle

Question 29

Knudson hypothesis

Answer 29

two-hits required for both copies of p53 to be knocked out

Question 30

Neurofilament (IHC)

Answer 30

neurons

Question 31

Asbestos

Answer 31

Lung CA and mesothelioma; but more lung CA

Question 32

Important features of tumor development (3) and role of immune system (2)

Answer 32

telomerase, angiogenesis, avoiding immune surveillance via downregulating expression of MHC class 1. reason why immunodeficiency increases risk for cancer

Question 33

Rb function and mutation

Answer 33

Rb has a leash on E2F (transcription factor required for G1 to S progression). Phosphorylation of Rb by cyclinD/CDK4 complex leads to freedom of E2F. mutation leads to E2F being constitutionally free = uncontrolled growth

Question 34

routes of mets (3)

Answer 34

1. Lymph- from carcinomas, travel to regional draining LN 2. Blood- from sarcomas, SOME carcinomas 3. Seeding of body cavities by ovarian CA (caking)

Question 35

p53 function

Answer 35

regulates progression of G1 to S by (1) inducing DNA repair if salvageable, (2) promoting apoptosis if jialat. Does so by producing BAX, which disrupts Bcl2, which stabilizes mitochondrial membrane. so cytochrome C leaks out, causing apoptosis

Question 36

how does RAS work as a _____

Answer 36

signal transducer. it is normally a/w GF receptor in its GDP-bound state. receptor binding replaces GDP with GTP, activating ras, and signal goes through. GAP cleaves phosphate group so GTP-->GDP. GAP is commonly mutated in neoplasia

Question 37

Ionizing radiation (RT or nuclear)

Answer 37

AML, CML, papillary carcinoma of thyroid; generates hydroxyl free radicals

Question 38

clinical features of benign (malignant) tumors (4)

Answer 38

slow growing(rapid), well-circumscribed(poorly), distinct(infiltrative) and mobile(fixed)

Question 39

xeroderma pigmentosum

Answer 39

restriction endonucleases don't work well, defective DNA repair = neoplasia

Question 40

S-100 (IHC)

Answer 40

melanoma, schwannoma, LCH

Question 41

Non-ionizing radiation (UVB sunlight)

Answer 41

BCC, SCC, melanoma; pyrimidine dimers in DNA normally excised by restriction endonuclease

Question 42

Vinyl cholride

Answer 42

Angiosarcoma of liver; PVC pipes from Home depot, plumbers

Question 43

Sporadic vs germline mutation of Rb

Answer 43

sporadic mutation leads to unilateral retinoblastoma, but germline results in familial retinoblastoma, 2nd hit somatic, leading to bilateral retinoblastoma and osteosarcoma

Question 44

c-MYC and explain

Answer 44

TF, uses t(8;14) involving IgH; a/w Burkitt lymphoma

Question 45

PDGFB

Answer 45

GR, uses overexpression and autocrine loop, astrocytoma

Question 46

Arsenic

Answer 46

SCC of skin, lung CA, angiosarcoma; used to be used to lighten skin, found also in cigarette smoke

Question 47

histological features of benign (malignant) tumors (6) and hallmark

Answer 47

organized growth (loss of polarity), uniform nuclei (nuclear pleopmorphism and hyperchromasia), low n:c ratio, minimal mitotic activity, lack of invasion, no METS

Question 48

4 carcinomas that spread hematogenously

Answer 48

1. HCC 2. RCC 3. Choriocaricnoma 4. Follicular CA of thyroid

Question 49

Alcohol

Answer 49

SCC of oropharynx and upper esophagus, HCC, pancreatic

Question 50

ABL

Answer 50

signal transducer, tyrosine kinase with t(9;22) with BCR, CLL and some types of ALL (ph+ALL)

Question 51

RAS gene family

Answer 51

Signal tranducer; GTP-binding protein; a/w carcinomas, melanoma and lymphoma

Question 52

RET (neural growth factor receptor)

Answer 52

GF-R, uses point mutation, MEN2A and MEN2B sporadic medullary carcinoma of thyroid

Question 53

Chromogranin (IHC)

Answer 53

neuroendocrine cells (SCCLC, carcinoid tumors)

Question 54

CDK4

Answer 54

cell cycle regulator, cyclin-dependent kinase, a/w melanoma

Question 55

n-MYC

Answer 55

TF, a/w neuroblastoma