Cancer Pathology, Colon Cancer; Exam 2

Front 1

What are some approaches to treatment of cancer?

Back 1

1) cytotoxic therapies
- cacner cells are prolif out of control, so we can use toxic drugs to growth of cells (standard chemo, radiation therapy)
"old methods"
side effects: can be toxic to normal cells
2) targeted therapies

Front 2

What are some examples of targeted therapies?

Back 2

1) targeting the oncogene
2) targeting the cell -fusion-txoin
3) target virus in EBV induced malignancies
4) target immune system
5) anti tumor vaccines, antibodies
6) gene therapy
7) interference w/ tumor progression or metasis

Front 3

Highest incidence of cancer for men? for women?

Back 3

Men: prostate (30%)
Women: breast (31%)

Front 4

Highest percentage of mortality for a cancer?

Back 4

Lung and bronchus for both men and women (25-31%)

Front 5

Major Risk factor for colorectal cancer?

Back 5

1) age especially (begins at age 50 and goes up exponentially until age 70)
*recommend colonscopy to those age 50 above*

Front 6

What part of the colon do most cancers develop?

Back 6

from the mucosa.
there's a precursor lesion that sits around for sometime = polyp (adenoma). Can sit here for 10 years before it turns into an invasive cancer (big window of opportunity)

Mean age at diagnosis: 67

Front 7

What happens if you leave a large polyp for a while?

Back 7

probability of growing into a cancer.

Front 8

National Polyp Study?

Back 8

Purpose: what's the purpose of a colonscopy. What effect does removing the polyps have on the incidence of colon cancer?

Results: those who had polypectomy had lower incidence of cancer than the general population. 70% less than expected

Front 9

2 molecular genetic pathways to colon cancer

Back 9

1. adenoma-carcinoma sequence/ APC - classical pathway. instigated by a homozygous deletion of tumor suppressor gene APC. associated w development of adenoma. driven by chormosomal instability.

50% of people over 50 have 1 or more polyps

2. Serrated Polyp pathway - BRAF or alternative pathway - totally different gene is mutated

Front 10

Crypts containing stem cells may lead to?

Back 10

start out as microscopic lesions, but slowly spread into the next crypt. eventually forms a small polyp.

blue in staining due to lots of DNA, and proliferation. constantly turning over, and APC mutation is associated with risk for develping chormosomal instability.

Front 11

What are 3 types of polyps that can be seen?

Back 11

1) peduncular
2) sessile
3) flat

Front 12

What are some types of adenomas

Back 12

1) tubular adenoma
2) villous adenoma

Front 13

After chromosomal mutation is considered to be instable, what leads to actual advanced adenoma?

Back 13

Acquires additional abnormalities, especially loss of p53/pLOH.

Front 14

Hybrid dysplasia?

Back 14

marks development of p53 mutation. causes the cell to undergo apoptosis. induces production of Bax

Front 15

When does KRAS mutation occur?

Back 15

usually in middle of pathway during advanced adenoma.

Front 16

What can you see in presence of large adenoma?

Back 16

18q, 6q, 22q, 8 p all involved in latter stages of abnormal cell growth; advanced cancer.

Front 17

Describe timeline of adenoma carcinoma sequence and their associated with the mutations

Back 17

1) aberrate crypt focus: APC
2) small adenoma: COX2
3) advanced adenoma: KRAS to p53
4) early cancer - p53 to 18q
advanced cancer - 8p, 6q, 22q

Front 18

ALternative pathway?

Back 18

Oncogene (activated mutation) occurs in BRAF (sometimes KRAS). This disturbs the RAS-RAF-MAP kinase pathway. Its present throughout cells and is the origin of cell growth and differentiation.

Front 19

Describe the oncogene induced senescence? (RAS-RAF-MAP-Kinase Pathway)

Back 19

- adaptive response that prevents cell transformation
2) upregulation of cell cycle inhibits p16, p14
3) upregulation of pro-apoptiotic proteins like RASSF!
4) inactivation is a potential mechanism for progression
5) effected by CpG island methylation or mutation

Front 20

Hyperplastic polyp?

Back 20

evolves during disordered growth.

Front 21

What is the instigator of the alternative pathway?

Back 21

promoter regions of genes get methylated on CpG island.

consequence; switches off growth control genes. eventually develops into a small cancer becuase HmLH1 gets mutated (its a mismatch repair gene).

Tandem repeats get typos; gene produces proteins that do not work. Eventually get microsatellite instability.

Front 22

What appearance of the colon whould you see in serrated adenomcarcinoma?

Back 22

BRAF-mut MSI cancer appears with diploid cells. Not driven by chormosomal instability, but driven by mistakes in microsatellites due to inactivation of hmlh1.

Get polymorphous appearance of cells

Front 23

What classficiation do we use for colorectal cancer?

Back 23

Dukes system
A - on the wall
B - penetrates pass the wall to underlying tissues
C- spreads to lymph nodes
D- distant mestasis

Front 24

What are some other minro determinants of progrnosis?

Back 24

stage, grade/differentiation, venous invasion, MSI>MSS, preopertive CEA level.

Front 25

What 2 things are in imbalance in cancer?

What's the main cause of cancer?

Back 25

Apoptosis (cell death) and proliferation (growth of cells) are in imbalance where proliferation exceeds apoptosis.

Damange to DNA causes it. Mutation may have important effects

Front 26

Describe some physical damage that occurs directly to DNA.

Back 26

-radiation (including sunlight/UV damage)
-chemicals (benzene, arsenic, chemo)
-environmental toxins (aryl HCs, formaldehyde)
-oxidant stress/free radicals

Front 27

What is aflatoxin?

Back 27

Made by a mold and found in nature as they grow on foodstuffs (esp grain, peanuts,etc). When ingested, its very toxic, and reacts with guanosine residues in DNA.

Front 28

What does the damage to DNA do functionally?

Back 28

this causes aberrant expression of genes...
-activation of genes that promote cell growth (proto-oncogenes turn into oncogenes - GFs, 2nd messengers, genes that prolong cell life Bcl-2 or immortalize cells Myc).
- suppression or mutation of genes that limit cell growth
-suppresion of genes that protect DNA from damage or muatios.

Front 29

What is one important tumor suppressor gene?

How does this interact with the cell cycle.

Back 29

Rb. This intercts with E2F, and it therefore inactivated. Cel cycle cannot procreed from one cell phase to another.

Front 30

Describe p53

Back 30

Another tumor supressor gene. G1 arrests, no S phase.

DNA repair genes attempt to repair the DNA.

absence of p53 = no cell cycle arrest, cells allowed to go through S phase and allowed to fixed mutations in genomes.

Front 31

What would you see present in the progression of normal colon to adenoma

Back 31

many DNA genes are missing such as hMSH2, hMLH. ras gene is mutationed
-very slow proces. multiple mutations occur in order to tumor to actually occur

Front 32

What must a tumor be able to do in order to proliferate?

Back 32

Needs to be able to grow in the absence of grwoth factors or growth signals.

-need to be insensitive to anti-proliferative signals.
-evade apoptosis
-replicate limitlessly
-sustained angiogenesis
-tissue invasion and mestasis

Front 33

what types of viruses cause cancer?

Back 33

-Hepatitis virus (liver cancer)
-human T cell leukemia virus
-Papilloma virus (cervical)
-Epstein Barr (lymphosas, NPC)
-Human herpes virus 8 (Kaposi's sarcoma)

Front 34

What are 3 general features of viral oncogenesis?

Back 34

-prevalence of infection is higher than incidence of associated tumor
-can initiate a multistage process of carcinogenesis
-tumor latency - requirement for accumulation of additional genetic changes mediating malignant progression

Front 35

What do viruses do regarding the normal stages of multi-step carcinogenesis?

Back 35

It bypasses the need for 1 or more steap usually involved in this process.

Front 36

What is viral latency?

Back 36

it goes into an episome or integrates into genome. or there just a subset of viral genes.

Front 37

What evidence is there that tumors may involve the immune system?

Back 37

can detect infiltation of tumors with lympocytes, macrophage/monocytes.

-increase incidence of cancers in immunosupressed states
-age, primary T cell immunodeficiencies, thyectomy, AIDS, post-trasplantation, radiation exposure, chemo, glucocorticoids

Front 38

What part of the immune system does NOT play a role in tumors

Back 38

B cell arm. No antibodies involved or complement system involved.

Phagocytes too

Front 39

What part of the immuno system does play a role in tumors?

Back 39

Natural killer cells CAN kill tumors
-they preexist
-regonized infected cells, tumor cells via killer inhibitory receptors. this is inhibited by MCH class 1 receptors. without these, it can work

Front 40

What role do cytotoxic T lymphocytes play in tumors?

Back 40

T lymphocytes has a dual restriction - self MHC and antigen. Not general.
-very specific and amplified after exposure to tumor.
-likely to be the most important defense we have.

Front 41

The most important determinant of outcome (prognosis) in pts with colorectal carcinoma is...

Back 41

tumor stage