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PH-SD15

Prognostic and predictive factors

What a cancer’s grade, stage, report features and molecular markers say about its likely course (prognostic factors) and about which treatments could work (predictive factors), why they differ, and their limits.

By the end, you can

  • Distinguish a prognostic factor from a predictive factor, and give an example that is both.
  • Explain what grade and stage each measure, and the parts of TNM staging.
  • Relate report features such as depth of invasion, lymphovascular invasion and margins to the mechanism of spread and recurrence.
  • Explain why a molecular marker can predict response to a drug that targets its pathway, and why a downstream mutation can cancel that.
  • Describe patient factors and the limits of all factors: probabilities for groups, sampling and heterogeneity.

What it is

A prognostic factor is a feature of the tumour or the patient that is associated with the likely course of the disease (recurrence, spread, survival), whatever treatment is given. A predictive factor is associated with benefit, or lack of benefit, from a particular treatment. Many features are one or the other; some, such as HER2 amplification in breast cancer, are both.

3 types to tell apart
Tumour factors
Type, grade, stage (TNM), depth of invasion, lymphovascular and perineural invasion, margins, and molecular features such as receptors, mutations and mismatch repair status.
Patient factors
Age, general fitness (performance status), other illnesses, nutrition and weight loss, and the immune and inflammatory response to the tumour.
Serum tumour markers
Substances in the blood made by or in response to a tumour (such as PSA, CEA, AFP, β-hCG); some help with staging or follow-up, none is a test for cancer on its own.

US spelling: tumour → tumor, oestrogen → estrogen, tumours → tumors.

Normal function

Normal cells: receptors, repair and differentiation

A normal epithelial cell divides only when told to. Growth factor receptors in the , such as the EGFR and HER2 family, pass signals through relay proteins (RAS, RAF and others) to the ; hormone receptors, such as the oestrogen receptor in breast and endometrium, act inside the nucleus to switch genes on. Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) correct the small copying errors made each time DNA is replicated.

Normal tissue also has a recognisable structure: glands, layers and cells that mature in order. That structure is the yardstick against which a pathologist judges how abnormal a tumour looks.

Tumours keep, amplify, mutate or lose these normal features. Measuring which they have done tells how the tumour is likely to behave and, for some features, which drugs could act on it.

Point to it on the model