Oncology

Question 0

Hypertrophy

Answer 0

Increase in the number of organelles and subsequently the size of cells

Question 1

Hyperplasia

Answer 1

Increase in the number of cells in an organ or tissue

Question 2

What cells can undergo hyperplasia

Answer 2

Cells capable of synthesizing DNA. Therefore, heart, skeletal muscle and nerve almost pure hypertrophy under stress or hormone stimulation

Question 3

Four types of hyperplasia

Answer 3

Physiologic
Hormonal (estrogen on endometrium)
Compensatory (liver after partial lobectomy)
Pathologic

Question 4

Define pathologic hyperplasia

Answer 4

Increase in cell number in response to external stimulus. Growth stops when stimulus abates (different to neoplasia) However, fertile ground for cancerous proliferation eg. Cervical cancer/endometrial

Question 5

Define choristoma

Answer 5

Excess of tissue in an abnormal location

Question 6

Define hamartoma

Answer 6

Benign disorganized tissue that grows at the same rate of surrounding tissue that is composed of tissue usually found at that site.

Question 7

Define metaplasia

Answer 7

A reversible change in which one adult cell type is replaced by another

Question 8

Define dysplasia

Answer 8

Disorderly but non-neoplastic tissue growth.

Often seen as precursor to carcinoma (‘in situ’)

Question 9

Dysplasia characterized by..

Answer 9

Ploemorphism
Hyperchromatism
Loss of normal orientation

Question 10

Define neoplasia

Answer 10

Abnormal growth of tissue that is virtually autonomous and exceeds that of surrounding tissue. Growth persists after cessation of stimuli.

Question 11

Two broad categories of neoplasia

Answer 11

Benign

Malignant

Question 12

Two broad categories of malignancy

Answer 12

Carcinoma

Sarcoma

Question 13

Factors used to differentiate beni and malignant tumours.

Answer 13

Differentiation/ anaplasia
Rate of growth
Local invasion
Metastasis

Question 14

Cytologic features that characterize anaplastic tumours

Answer 14

Nuclear and cellular pleomorphism
Hyperchromatism
Nuclear:cytoplasmic ratio approaches 1:1
Abundant mitoses
Tumour giant cells
Disarray of tissue architecture

Question 15

Three routes of distant spread by tumours

Answer 15

Into body cavities eg. Transperitoneal
Invasion of lymphatics
Haematogenous

Question 16

Most likely route of spread of carcinomas

Answer 16

Lymphatic

Question 17

Most likely route of spread of sarcomas

Answer 17

Blood

Question 18

Two causes of LN enlargement in metastatic carcinoma

Answer 18

Proliferation of carcinoma cells

Reactive hyperplasia in response to Ags

Question 19

Six hallmarks of cancer

Answer 19

Limitless replicative potential
Self sufficiency in growth signals
Insensitivity to anti growth signals
Evades apoptosis
Sustained angiogenesis
Tissue invasion and metastisis

Question 20

Two emerging hallmarks of cancer

Answer 20

Deregulating cellular energetics

Avoiding immune destruction

Question 21

Two enabling characteristics

Answer 21

Genome instability and mutation

Tumour-promoting inflammation

Question 22

What is the generally accepted model of tumorigenesis

Answer 22

Multi step and multigene

Question 23

Why is RAS a good candidate for being involved in cancer

Answer 23

Has many downstream effects and is involved in many cellular processes

Question 24

Examples of mechanisms for each hallmark of cancer

Answer 24

Self sufficient growth signals - activate H-Ras oncogene Insensitive to anti growth signals - lose Rb suppressor Evade apoptosis - produce IGF survival factors Limitless replication - turn on telomerase Sustained angiogenesis - produce VEGF inducer Invasion/ metastasis - inactivate E-cadherin

Question 25

Factors that cause cancer

Answer 25

Hereditary Chemicals Radiation Viral/bacterial

Question 26

End points of DNA damage

Answer 26

Repair and cell survival Block replication -> apoptosis Gene/chromosomal change -> cancer

Question 27

Normal regulation of G1/S control point

Answer 27

CyclinD/cdk4,6 complex phosphorylates Rb.E2F. Rb.E2F is then further phosphorylated by cyclinE/cdk2 which causes release of E2F and the subsequent transcription of proliferation genes.

Question 28

How HPV causes cancer

Answer 28

E6 inactivates p53 therefore less p21 E7 causes E2F release from Rb Therefore proliferation despite DNA damage

Question 29

Process of metastisis

Answer 29

Break BM, induce angiogenesis, invade blood or lymph, adhere to cap wall in target tissue, invade normal tissue, proliferate forming 2ndry tumour(more angiogenesis)

Question 30

Various products formed by cisplatin

Answer 30

Intrastrand cross link Interstrand cross link Monoadducts (either with one monoadduct still available for reaction or monoadduct linked to small molecule or nuclear protein)

Question 31

Mutations in these gene classes can lead to cancer

Answer 31

Tumour suppressor Protooncogenes DNA repair genes Cell cycle genes

Question 32

Define microsatellites

Answer 32

Highly conserved, stably inherited, short tandem repeats/motifs

Question 33

Increase or decrease in microsatellites =

Answer 33

Microsatellites instability (MSI)

Question 34

MSI arises due to..

Answer 34

DNA slippage Backward slippage = more repeats Forward slippage = less repeats

Question 35

Name DNA repair genes

Answer 35

MLH1 MSH2,3,6 PMS1,2

Question 36

How DNA repair genes work

Answer 36

``` Binds incorrect pairing or adduct. Helicase unwinds DNA Endonuclease 'cuts' out fragment DNA polymerase fills the gap DNA lipase reseals remaining nick ```

Question 37

How is MSI tested for

Answer 37

DNA extracted from normal and tumour tissue. Amplify DNA with PCR Add Bethesda markers. Analyse fragment sizes If loss of heterozygosity = MSI (Can only be done in heterozygotes)

Question 38

Knudson's two hit hypothesis

Answer 38

Loss of tumour suppression requires LOF of both alleles of a relevant gene

Question 39

What is the Fearon and Vogelstein pathway

Answer 39

The adenoma-carcinoma sequence that is caused by sequential genetic alterations (clonal evolution) that causes colorectal cancer. Possible 5-hit scenario [5q mutation, DNA hypo methylation, 12p = k-Ras mutation, 18q loss, 17p = p53 loss)

Question 40

What is the other genetic pathway in CRC other that FV

Answer 40

MSI

Question 41

What CRCs is MSI seen in

Answer 41

HNPCC - hereditary nonpolyposis colorectal cancer | Sporadic CRC

Question 42

Clinical description of HNPCC

Answer 42

``` Inherited Early onset Multiple Mutation in MMR Accelerated adenoma to carcinoma Right sided Mucinous with signet cells ```

Question 43

Three types of MSI status

Answer 43

MSS MSI-L MSI-H

Question 44

Two forms of instability in MMR

Answer 44

CIN | MSI

Question 45

What is CIN

Answer 45

Chromosome instability. Many chromosomal abnormalities Linked to APC mutations Mediated by stepwise accumulation of cytogenetic changes

Question 46

How does one test for MMR gene defects

Answer 46

Direct test of hMSH2 and hMLH1 Indirect staining for hMSH2 and hMLH1 proteins MSI test (Bethesda markers)

Question 47

Sporadic MSI + CRC due to..

Answer 47

Promotor hypomethylation of hMLH1 NB NO MUTATION, common in elderly/female

Question 48

HNPCC MSI+ tumours due to..

Answer 48

Germline mutation of DNA MMR gene Early onset

Question 49

What is MSI-H termed

Answer 49

Lynch syndrome associated MSI

Question 50

Two classes of chemical carcinogens

Answer 50

Genotoxic | Non genotoxic

Question 51

Possible drug targets for anti metastisis

Answer 51

Molecules over expressed (tenascin-C) Intracellular signaling (rac/rho) Provide anti motility signals (CXCR3, decorin)