Immunohistochemistry & Biomarker Staining

What It Measures

• Oestrogen Receptor (ER) and Progesterone Receptor (PR) — hormone therapy eligibility
• HER2 protein expression (scored 0, 1+, 2+, 3+) — Herceptin/trastuzumab eligibility
• PD-L1 expression (TPS and CPS scores) — pembrolizumab, atezolizumab, durvalumab eligibility
• Ki-67 proliferation index — tumour aggressiveness and chemotherapy need
• ALK, ROS1 rearrangements (confirmed by FISH or IHC screening)
• Mismatch Repair proteins (MLH1, MSH2, MSH6, PMS2) — dMMR/MSI-H predicting immunotherapy benefit
• CD20 (lymphoma) — rituximab eligibility
• BRAF V600E mutation (IHC screening) — BRAF inhibitor eligibility in melanoma and CRC
• Androgen Receptor (AR) in breast and prostate cancer
• P53 aberrant expression, SMAD4 loss, and other prognostic markers

How It Works

Tumour tissue fixed in formalin and embedded in paraffin (FFPE) is cut into thin sections (4 microns) and mounted on slides. A primary antibody specific to the target protein is applied, followed by a secondary antibody linked to a colour-producing enzyme or fluorescent label. A pathologist examines the stained slides under a microscope and scores the intensity and proportion of stained cells according to validated scoring systems (Allred score for ER, HercepTest scoring for HER2, TPS/CPS for PD-L1). Digital pathology AI platforms increasingly assist with automated scoring.

• All newly diagnosed cancer patients — IHC is a standard component of initial pathology reporting
• Patients receiving results from a biopsy who want to understand what the markers mean
• Those being considered for immunotherapy — PD-L1 and dMMR status are essential
• Breast cancer patients — ER, PR, HER2, Ki-67 determine the entire treatment pathway
• Any patient changing treatment line — re-biopsy IHC may reveal receptor conversion

IHC is not an emerging test — it is the established standard of care and has been so for decades. ER/PR testing in breast cancer has been guideline-standard since the 1980s. HER2 testing with Herceptin has transformed outcomes in HER2+ breast cancer (HERA trial: 50% reduction in recurrence). PD-L1 testing for pembrolizumab is FDA-required for NSCLC, HNSCC, TNBC, esophageal cancer, and others. dMMR/MSI-H testing is now recommended universally for all colorectal cancers and increasingly for all solid tumours given the MSI-H pembrolizumab approval (KEYNOTE-158). IHC results directly determine drug eligibility in the majority of solid tumour types.

This list is not exhaustive. Ask your oncologist or integrative physician for locally available options.

• HER2 IHC 2+ results are equivocal and MUST be confirmed with FISH (fluorescence in situ hybridisation)
• PD-L1 scoring varies by antibody clone and assay platform — SP142, 22C3, 28-8 clones are not interchangeable across cancer types
• Tumour heterogeneity means one biopsy area may not reflect the whole tumour's marker status
• Receptor conversion (ER positive → negative at metastasis) occurs in 10–30% of breast cancers — re-biopsy is important at progression
• Ki-67 scoring has high inter-observer variability — standardised digital pathology is preferred