A biomarker is a measurable biological characteristic that provides information about a normal or abnormal biological process. In pathology, biomarkers are typically proteins, or the genes that encode them, whose presence, absence, or expression level in tumor tissue carries clinical meaning.
Biomarkers are used to classify tumors when morphology alone is ambiguous, predict prognosis where certain biomarker profiles are associated with more or less aggressive disease, and guide treatment selection where many targeted therapies and immunotherapies are only effective in tumors expressing a specific biomarker.
IHC is one of the primary methods for measuring biomarker expression in tissue. The pathologist applies an antibody targeting the biomarker of interest to a stained slide and evaluates the result based on the intensity of staining, the percentage of cells staining positive, and the location of the signal within the cell (nuclear, cytoplasmic, or membranous).
Different biomarkers use different scoring systems. Some are reported as positive or negative. Others use a continuous scale such as the H-score (0 to 300), which combines staining intensity and the percentage of positive cells. The scoring system used depends on the biomarker and the clinical question being asked.
p53 is a tumor suppressor protein encoded by the TP53 gene. IHC patterns (null, wildtype, overexpressor) reflect the underlying mutation status and are used in cancer classification and research. MLH1, MSH2, MSH6, and PMS2 are mismatch repair (MMR) proteins. Loss of nuclear expression of one or more of these proteins indicates deficient mismatch repair (dMMR), which has implications for immunotherapy eligibility. PD-L1 is a checkpoint protein whose expression level in tumor cells and immune cells is used to predict response to checkpoint inhibitor therapies. HER2 is a receptor protein that, when overexpressed, makes certain breast and gastric cancers eligible for HER2-targeted therapy.
Biomarker results from one laboratory need to be comparable to results from another, especially in clinical trials where patients are enrolled across multiple sites. Inconsistent antibody concentrations, staining protocols, or scoring criteria can produce different results from the same tissue, affecting which treatment a patient receives. Standardized controls, validated antibodies, and objective scoring tools are all part of ensuring biomarker results are reproducible and clinically reliable.