HER2: Biology, Definition, Diagnosis, and its Role in Cancers

Amplification or overexpression of the transmembrane epidermal growth factor receptor 2 (HER2) oncogene (also known as c-erbB-2) is a well-established driver of carcinogenesis and a negative prognostic factor across multiple cancer types. Its intracytoplasmic tyrosine kinase domain activates intracellular signaling pathways that promote tumor proliferation, disrupt cell-cell adhesion, and enhance invasiveness. HER2-amplified cancers demonstrate aggressive clinical behavior due to their inherent metastatic potential, correlating with reduced overall survival rates. Immunohistochemistry (IHC) remains the primary method for detecting HER2 protein overexpression in tumor tissues, with results categorized as positive, equivocal, or negative based on standardized scoring criteria. Complementary techniques such as fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) are critical for confirming HER2 gene amplification. These methods form the cornerstone of diagnostic protocols not only in breast cancer but also in HER2-positive advanced gastric, colorectal, and endometrial malignancies. Accurate HER2 status determination through guideline-adherent testing is essential for therapeutic decision-making. HER2-targeted therapies, including monoclonal antibodies and tyrosine kinase inhibitors, have demonstrated efficacy as neoadjuvant/adjuvant treatments and as systemic therapies for unresectable or metastatic disease. Standardized biomarker testing and targeted intervention strategies hold significant potential to improve survival outcomes in HER2-driven cancers.