Neoplasia introduction

Question 1

What is the multistep model in terms of carcinogensis?

Answer 1

Cancers arise from stepwise accumulation of mutations

predisposing factors (tumour suppressor genes, oncogenes), environmental factors (eg. chronic inflammation - H.pylori), age

synergistic effects

Question 2

What are the steps in a mulitstep model in carcinogenesis?

Answer 2

1. initiation

permanent non-lethal DNA damage

• Add on effect, irreversible
• chemical/ microbial/ physical
• Carcinogens/produce electrophiles/form DNA adducts/mutagens

2. Promotion
   DNA-damaged cells have survival advantage > proliferation advantage

• reversible
• Mitogens: hormones/Growth factors/phorbol esters/chronic inflammation

3. Progression
   Selection for aggressive phenotypes- genetic evolution

Question 3

Name 8 hallmarks of cancer

Answer 3

1. sustain proliferative signalling (self-sufficiency)
2. ignore growth suppressors
3. evade apoptosis
4. immortality
5. angiogenesis
6. invasion & metastasis
7. altered Energy metabolism
8. evade immune destruction

Question 4

What are some infectious agents that can cause cancer?

Answer 4

HPV
carry E6 and E7 protein oncogene- promote tumor growth and malignant transformation

Tumourgenic progress- alterations in DNA copy number

Epstein-Barr virus (EBV)
potent growth-transforming agent for primary Burkitt’s cells

c-myc translocation
Burkitt’s lymphoma

H. pylori
gastric adenocarcinoma

Question 5

What are the steps in tumour development?

Answer 5

cell with mutation > hyperplasia > dysplasia > carcinoma in situ > invasive cancer

Question 6

What is dysplasia?

Answer 6

Abnormality in growth and maturation of cells within a tissue (pre-cancerous)

eg. colonic polyps

Question 7

What stage in tumour growth (dysplasia etc) is BPH classified as?

Answer 7

Hyperplasia

Question 8

What is carcinoma in situ

Answer 8

cells have dedifferentiated with invasive potential

Question 9

What do you call when a Normal cell layer is replaced by a cell type not normally found in that location

Answer 9

metaplasia

• microscopically normal otherwise
• often in transition zones (cervix-uterus, oesophagus-stomach)

Question 10

List 6 abnormal nuclear morphological changes of carcinoma

Answer 10

1. hyperchromasia
2. chromatin clumping
3. prominent nucleoi
4. high mitotic rate
5. little cytoplasm (due to increase nuclear size)
6. high nuclear: cytoplasmic ratio (>1:5)
7. abnormal nuclear shape/size (pleomorphism)

Question 11

Name 3 histological features of abnormal cell division in cancer

Answer 11

increased mitotic rate

increased mitotic figures

multipolar spindle

Question 12

What is pleomorphism?

Answer 12

change in cell shape and size

Question 13

What is anaplasia?

Name 7 features of anaplasia

Answer 13

cells that have de-differentiated too quickly to determine tissue of origin

1. pleomorphism
2. abnormal nuclear size (increase)
3. necrotic centre
4. abnormal morphology
5. abnormal mitosis
6. loss of polarity
7. tumour giant cells