Foundation - Oncology

Question 1

Define cancer

Answer 1

The development of cells that divide uncontrollably and have the ability to infiltrate and destroy normal body tissues

Question 2

Name the most common cancers in Singapore

Answer 2

Men: prostate, colorectal, lung
Women: breast, colorectal, lung
Children: acute lymphocytic leukaemia

Question 3

Define the following terms:
(i) Dysplasia
(ii) Metaplasia
(iii) Neoplasia
(iv) Anaplasia

Answer 3

(i) Abnormal changes in size, shape and/or organisation of cell
(ii) Change in cell type due to change in cell stress
(iii) Abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue + persists after stimulus disappears
(iv) Lack of cell differentiation

Question 4

Describe the histological features of malignant cells

Answer 4

1. Hyperchromasia (darker than normal appearance)
2. Pleomorphism (diff sizes and shapes)
3. High nuclear: cytoplasmic ratio
4. High mitotic index
5. Coarse, clumped chromatin, irregularly distributed
6. Enlarged, abnormally shaped, multiple nucleoli
7. Metastasis
8. Anaplasia
9. Necrosis and haemorrhage
10. Infiltrative growth

Question 5

Distinguish between the microscopic features of benign and malignant neoplasms

Answer 5

1. Benign resembles normal tissue of origin VS malignant does not
2. Benign has few mitoses vs malignant has increased mitotic activity often with abnormal mitotic figures present
3. Benign is highly differentiated vs malignant is poorly differentiated
4. No metastasis vs metastasis to distant sites
5. Well-formed vs poorly-formed blood vessels
6. Normal-looking cells VS cytologic abnormalities (irregular nuclei, pleomorphism)
7. Pink vs purple appearance (highly eosinophilic)

Question 6

Describe the origin of the following
(i) Carcinoma
(ii) Sarcoma
(iii) Adeno
(iv) Leimyo
(v) Papillo
(vi) Rhabdomyo
(vii) Blastomas

Answer 6

(i) Epithelial tissues (derived from ectoderm/endoderm)
(ii) Connective tissue (derived from mesoderm)
(iii) Glandular
(iv) Smooth muscle
(v) Papillary
(vi) Striated muscle (ie skeletal/cardiac)
(vii) Primitive blast cells/progenitor cells

Question 7

Most of the ‘-oma’s are benign except

Answer 7

Malignant lymphomas, melanomas, gliomas, myelomas, teratomas, carcinoma

Question 8

Define carcinoma in situ

Answer 8

Limited region of cells showing dysplasia but has not spread past basement membrane

Question 9

Why are there adenocarcinomas but not adenosarcomas?

Answer 9

There are glands in epithelium but not in connective tissue

Question 10

Define small cell carcinoma

Answer 10

Malignant epithelial neoplasm, characterised by small size of cancer cells
Most commonly associated with lung cancer

Question 11

Name the 10 hallmarks of cancer

Answer 11

1. Growth signal autonomy
2. Insensitivity to growth inhibitory signals
3. Evade apoptosis
4. Angiogenesis
5. Invasion and metastasis
6. Reprogramming energy metabolism
7. Unlimited replicative potential
8. Avoid immune destruction
9. Genetic instability
10. Tumour-promoting inflammation

Question 12

Describe normal cell proliferation

Answer 12

1. Binding of growth factor to specific receptor
2. Transient and limited activation of growth factor receptor
3. Cascade of biochemical events with eventual signal transduction to nucleus
4. Induction and activation of nuclear regulatory factors that initiate transcription
5. Expression of genes involved in cell growth and cell cycle progression

Question 13

Describe the pathogenesis of chronic myeloid leukaemia, relating to the hallmark of growth signal autonomy

Answer 13

Reciprocal translocation between chromosomes 9 and 22 → formation of Philadelphia chromosome with BCR-ABL1 fusion gene → encode hybrid tyrosine kinase with increased enzymatic activity → unregulated HSC proliferation → differentiated into mature myeloid cells

Question 14

Describe the pathogenesis of Burkitt lymphoma, relating to the hallmark of growth signal autonomy

Answer 14

t(8;14) translocation mutation → upregulation of c-myc gene → master transcription factor that activates many genes involved in cell growth

Question 15

Describe the pathogenesis of Hairy cell leukaemia/ CRC, relating to the hallmark of growth signal autonomy

Answer 15

Upregulation of RAS (KRAS, NRAS, HRAS)/RAF (BRAF) family genes → amplification of cell signalling molecules

Question 16

Describe the pathogenesis of lung adenocarcinoma in female non-smokers, relating to the hallmark of growth signal autonomy

Answer 16

Epidermal growth factor receptor (EGFR) point mutation and exon 19 deletion → conf change such that it is constitutionally active → activate growth factors involved in cell cycle progression

Question 17

Describe the pathogenesis of glioblastoma, relating to the hallmark of growth signal autonomy

Answer 17

Amplification of platelet-derived growth factors (PDGF)

Question 18

Describe the pathogenesis of breast cancer, relating to the hallmark of growth signal autonomy

Answer 18

Amplification of HER2

Question 19

Describe the pathogenesis of retinoblastoma, relating to the hallmark of growth signal autonomy

Answer 19

Cyclins have 1 GOF mutation → bind to cyclin-dependent kinase → form cyclin-CDK complex → cyclin-CDK phosphorylates and fluctuates Rb → progression of cell cycle from G1 to S and beyond → uncontrolled cell proliferation

Question 20

Describe the pathogenesis of retinoblastoma, relating to the hallmark of insensitivity to growth inhibitory signals

Answer 20

Retinoblastoma protein undergo 2 LOF mutations → cannot bind to E2F transcription factor needed to regulate transcription → E2F can initiate transcription of genes needed for DNA replication → progression of cell cycle from G1 to S and beyond → uncontrolled cell proliferation

Question 21

Describe the pathogenesis of familial adenomatous polyposis (FAP), relating to the hallmark of insensitivity to growth inhibitory signals

Question 22

Describe the pathophysiology of cancer cells having unlimited replicative potential

Answer 22

Usually, cells go into senescence when their telomeres reach Hayflick limit
However, cancer cells reactivate telomerase → lengthen and maintain telomeres → replicative immortality

Question 23

Outline the invasion-metastasis cascade that enables the cancer cells to spread

Answer 23

1. Tumour cells dissociate from tumour mass by inactivating E-cadherin
2. Gain mobility via epithelial-mesenchymal transition → loss of polarity and cell-cell adhersion
3. Secreting proteolytic enzymes (e.g. matrix metalloproteinases)
4. Underlying basement membrane breached
   5.