Principles of Neoplasia

Principles of Neoplasia

Definitions

• Neoplasm: autonomous abnormal new growth that persists after the initiating stimulus is removed
• Benign: localised, well-differentiated, no invasion or metastasis, low mitotic rate
• Malignant: invasive, potential to metastasise, often poorly differentiated, high mitotic rate

Hallmarks of Cancer (Hanahan & Weinberg)

1. Sustaining proliferative signalling
2. Evading growth suppressors (tumour suppressor genes, e.g. RB, TP53)
3. Activating invasion & metastasis
4. Enabling replicative immortality (telomerase)
5. Inducing angiogenesis (VEGF)
6. Resisting cell death (anti-apoptotic: BCL-2)
7. Deregulating cellular energetics (Warburg effect)
8. Avoiding immune destruction

Oncogenes vs Tumour Suppressor Genes

| | Oncogene | TSG |

|-|----------|-----|

| Normal function | Promotes cell division | Restrains division, promotes apoptosis |

| Mutation type | Gain-of-function (one allele) | Loss-of-function (both alleles — Knudson 2-hit) |

| Examples | RAS, MYC, HER2 | RB1, TP53, BRCA1/2 |

Routes of Metastasis

• Lymphatic: carcinomas (first to regional nodes)
• Haematogenous: sarcomas, also carcinomas (liver, lung, bone, brain common sites)
• Transcoelomic: ovarian → peritoneum
• Perineural: prostate, pancreatic

Tumour Grading vs Staging

• Grade: degree of differentiation (G1 well-differentiated → G3/G4 poorly differentiated)
• Stage: extent of spread (TNM: tumour size, node involvement, metastasis)