Neoplasia

Question 1

Contrast the general features of benign vs malignant tumours

Answer 1

Benign: locally expansile, slow growth, often well circumscribed (+/- capsule), well differentiated cells, unable to metastasise
Malignant: locally invasive, often poorly circumscribed, can be necrotic, variable differentiation, potential to metastasise

Question 2

What are the 3 main modes of metastasis?

Answer 2

Lymphatic
Haematogenous
Transcoelomic (through membranes)

Question 3

List 8 histopathological features of neoplasia

Answer 3

Large nuclei
Pleomorphic nuclei (vary in size and shape)
Coarser nuclear chromatin
Hyperchromatic nuclei
Prominent nucleoli
Abnormal mitotic figures
Architectural disorganisation
Desmoplastic stroma

Question 4

What are anaplastic cells?

Answer 4

Completely undifferentiated cells

Question 5

What prefix is used for a glandular tumour?

Answer 5

Adeno

Question 6

What prefix is used for a smooth muscle tumour?

Answer 6

Leiomyo

Question 7

What prefix is used for a osteoblastic (osteoid-forming) tumour?

Answer 7

Osteo

Question 8

What suffix is used for a benign tumour?

Answer 8

-oma (there are some exceptions to this, e.g. lymphoma)

Question 9

What suffix is used for a malignant epithelial tumour?

Answer 9

Carcinoma

Question 10

What suffix is used for a malignant mesenchymal tumour?

Answer 10

Sarcoma

Question 11

What are 2 characteristic histological features of glandular tumours?

Answer 11

Formation of glandular lumina

Signet ring cells producing mucin

Question 12

What are 3 characteristic histological features of squamous cell tumours?

Answer 12

Eosinophilic cytoplasm
Keratinisation
Intercellular bridges

Question 13

What does tumour grade measure?

Answer 13

Degree of differentiation

Question 14

What is an in situ carcinoma?

Answer 14

Generally refers to severe (grade 3) dysplasia

Question 15

How do neoplasms invade past the basement membrane?

Answer 15

Can degrade the BM via release of matrix metalloproteinases

Question 16

When are polyps commonly formed?

Answer 16

When glandular dysplastic lesions occur in epithelia lining organs

Question 17

What are the 4 classes of normal regulatory genes relevant to carcinogenesis?

Answer 17

Growth-promoting proto-oncogenes
Growth-inhibiting TSGs
Genes regulating apoptosis
DNA repair genes

Question 18

Give 3 examples of TSGs

Answer 18

p53
Rb
APC

Question 19

Give 3 examples of oncogenes

Answer 19

HER2
Ras
Myc

Question 20

Given an example of a DNA repair gene

Answer 20

BRCA (1, 2)

Question 21

What is the difference between a mutation and a polymorphism in cancer genetics?

Answer 21

Mutation: any change in a DNA sequence away from normal (implies there is a normal allele that is prevalent in the population), involved in pathogenesis of cancer
Polymorphism: DNA sequence variation common in the population (no single allele is considered standard), influences RISK of cancer

Question 22

What is responsible for the slow progression in low growth fraction tumours?

Answer 22

Cell production vs. death occurs at a similar rate

Question 23

Give 3 examples of high growth fraction tumours

Answer 23

Leukaemias
Lymphomas
Small-cell carcinoma

Question 24

Give 2 examples of low growth fraction tumours

Answer 24

Colon

Breast adenocarcinoma

Question 25

What are oncogenes?

Answer 25

Mutant versions of proto-oncogenes that function autonomously without a requirement for normal growth-promoting signals

Question 26

Give 5 examples of common (normal physiological) roles of oncogenes

Answer 26

``` Growth factors (acting in autocrine manner) Growth factor receptors Signal transduction proteins TFs Cyclins and CDKs ```

Question 27

What is loss of heterozygosity (LOH)?

Answer 27

Loss of normal function of 1 allele of a gene in which the other allele was already inactivated

Question 28

What is p53 and what is its role?

Answer 28

TF which can regulate the expression of cell cycle factors | Involved in apoptosis, cell-cycle arrest, DNA repair, differentiation and senescence

Question 29

What are some of the mechanisms regulating TSG expression?

Answer 29

miRNA-mediated control | Epigenetic control

Question 30

What are 6 mechanisms used by neoplasms to evade apoptosis?

Answer 30

IMAGE Reduced CD95 level Inactivation of death-induced signalling complex by FLICE protein Upregulation of anti-apoptotic Bcl-2 Reduced levels of pro-apoptotic BAX resulting from loss of p53 Loss of APAF-1 Upregulation of inhibitors of BAX

Question 31

How do tumour cells develop immortality?

Answer 31

Via reactivation of telomerase

Question 32

What is the molecular mechanism underlying metastasis?

Answer 32

Detachment: via disruption of cellular "glue" (cadherins, beta-catenin, connexins) Degradation of ECM Attachment to novel ECM components Migration of tumour cells

Question 33

What are some popular therapeutic targets for cancer and what is the role of these targets?

Answer 33

VEGFs, VEGF receptors | Involved in tumour angiogenesis

Question 34

List 10 characteristics of tumours and the classes of therapeutics used to target them

Answer 34

Sustaining proliferative signalling: EGFR inhibitors Evading growth suppressors: CDK inhibitors Avoiding immune destruction: immune-activating anti-CTLA4 mAb Enabling replicative immortality: telomerase inhibitors Tumour-promoting inflammation: selective anti-inflammatory drugs Activating invasion and metastasis: inhibitors of HGF/c-Met Inducing angiogenesis: inhibitors of VEGF signalling Genome instability and mutation: PARP inhibitors Resisting cell death: pro-apoptotic BH3 mimetics Deregulating cellular energetics: aerobic glycolysis inhibitors

Question 35

What causes weight loss and anorexia in cancer?

Answer 35

TNF-a, IL-1 produced by tumour cells or cells in the tumour microenvironment

Question 36

What are the 4 important diagnostic/prognostic factors to determine following a diagnosis of malignancy?

Answer 36

Specific tumour type and subtype (cell lineage) Grade Stage Presence of lymphovascular invasion

Question 37

What does tumour stage measure?

Answer 37

Refers to the progression the malignancy has made in terms of local spread and metastasis

Question 38

What is the most common staging system used?

Answer 38

TNM

Question 39

What are the criteria of the TNM staging system?

Answer 39

T: extent of primary tumour (T0-T4 indicating size and local extent) N: regional LN metastases (N0-N3) M: absence or presence of distant metastases (M0-M1) X indicates cannot be assessed or unknown Components are combined to give a stag grouping, usually from I-IV

Question 40

What are some prognostic factors in cancer?

Answer 40

Vascular invasion seen in primary tumour | Specific genetic alterations

Question 41

What are the 2 main categories of targeted therapies for cancer?

Answer 41

Small molecules that e.g. inhibit GF receptors or TK | Monoclonal antibodies that target specific proteins or receptors

Question 42

When does metaplasia arise?

Answer 42

Response to chronic injury (e.g. GORD, chronic gastritis, chronic inflammation, smoking) Can be physiological (e.g. cervical transformation zone)