Tumour markers used in the diagnosis and prognosis of cancer

biomarkers clinical purposes

• risk

• diagnosis

• prognosis

• monitoring

risk

Estimates inherited or acquired

predisposition. Example: a pathogenic

germline BRCA1 or BRCA2 variant.

diagnosis

Supports detection or defines tumour

type. It rarely works safely as an

isolated result.

prognosis

Estimates outcome, or identifies likely

benefit from a specified treatment.

monitoring

Tracks response, residual disease or

recurrence when the marker is

informative for that tumour

specimen and method shape interpretation

• circulating markers

• tissue biomarkers

• germline testing

circulating markers

Proteins, hormones or

tumour-derived

material in blood or

urine. Examples

include PSA, CA125,

CEA and hCG.

tissue biomarkers

Histology, immunohistochemistry, in-situ hybridisation or sequencing can define receptors and genomic alterations.

germline testing

Usually blood or saliva;

identifies inherited

variants with

implications for the

patient and relatives.

diagnostic markers

• enzymes and proteins

• hormones and hormone receptor

• genetic and molecular markers

• circulating tumour cells

enzymes and proteins

Bladder cancer, measured in urine to monitor progression and response to treatment

hormones and hormone receptors

Neuroendocrine tumours affecting the pancreas or gastrointestinal tract (GEP-NETs), diagnostic imaging of

Somatostatin receptor to help determine treatment

Human chorionic gonadotropin (hCG): elevated in

some testicular and ovarian cancers.

• Glycoprotein produced in pregnancy by the

placenta >> presence in urine = +pregnancy test

genetic and molecular markers

Present in some Leukemias’ mutation present in blood and bone marrow confirms diagnosis

Mutations in BRCA1 and BRCA2: Associated

with increased risk of breast and ovarian

cancer.

circulating tumour cells

Found in blood samples of metastatic breast, prostate, and colorectal cancers used to inform clinical decision

making, and to assess prognosis

germline risk and tumour prediction

• germline variant

• somatic tumour finding

• therapeutic relevance

germline variant

An inherited pathogenic variant can alter lifetime cancer risk and has implications for surveillance, prevention andrelatives.

somatic tumour finding

An alteration detected in the tumour may be acquired and can inform treatment without necessarily being inherited.

therapeutic relevance

BRCA-associated

homologous

recombination

deficiency may predict

benefit from PARP

inhibition in defined

cancers and pathways.

liquid biopsy: promise and boundaries

• circulating tumour cells

• circulating tumour DNA

  • clinical readiness

circulating tumour cells

Intact tumour-derived cells can offer prognostic information and material for analysis, but capture is technically difficult.

circulating tumour DNA

Tumour-derived DNA fragments can reveal alterations and sometimes monitor tumour burden or resistance.

Clinical readiness

Utility depends on

tumour shedding,

assay performance,

timing and evidence

that acting on the

result improves

outcomes.

prognostic markers

A prognostic biomarker is a clinical or biological characteristic that provides information on the

likely patient health outcome (e.g. disease recurrence, progression free and overall survival),

irrespective of the treatment

1. HER2/neu: Predicts breast cancer prognosis and response to targeted therapy.

2. Ki-67: Indicates proliferation rate and predicts cancer aggressiveness.

3. B-Type Natriuretic Peptide (BNP): Prognostic marker for lung and other cancers

Human epidermal growth factor receptor 2 ( HER2) HER2/ net oncogene

30% of breast cancers have an amplification of the HER2/neu

gene or overexpression of its protein product.

• Overexpression of this receptor in breast cancer is

associated with increased disease recurrence and worse

prognosis.

• Because of its prognostic role as well as its ability to predict

response to trastuzumab (Herceptin) breast tumours are

routinely checked for overexpression of HER2/neu

Ki- 67 index test

The grade of a large bowel or rectal neuroendocrine

tumour (NET) tells you how much the cancer cells

look like normal cells under a microscope.

• The Ki-67 or mitotic index are ways of describing

how many cells are dividing

• A stain measures the Ki-67 value by counting % of

cells undergoing mitosis thus actively proliferating

• UK uses WHO grading 1 to 3

• The grade of your cancer helps your doctor decide

which treatment you need

limitation of cancer cell markers

Poor sensitivity and specificity – screening not possible

• Lack specificity to tumour type

• Many are endogenous and altered in non-cancerous conditions

• Expression/mutation etc may not be altered in all patients with the same cancer

• Some cancers (to date) lack specific tumour marker