DOI: 10.4103/aam.aam_508_26 ISSN: 1596-3519

Clinicopathological and Prognostic Impact of Human Epidermal Growth Factor Receptor 2 Overexpression in Gastric Carcinoma

Shivam S. B. Sharma Gaur, Shilpa T. Patil, Thumma Amar
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Abstract

Background:

Gastric carcinoma is the fifth-most common cancer worldwide and the third-leading cause of cancer-related deaths, with a 5-year survival rate of approximately 20%. Human epidermal growth factor receptor 2 (HER2) overexpression occurs in 10–30% of gastric and gastroesophageal junction adenocarcinomas and acts as a key prognostic and predictive biomarker, similar to breast cancer. Encoded by the ERBB2 gene, HER2 is a transmembrane tyrosine kinase receptor that promotes cell proliferation, survival, and differentiation via phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase pathways. In gastric cancer, HER2 expression is often heterogeneous and incomplete, which complicates diagnostics and is linked to aggressive features such as intestinal histology, advanced stage, and poor survival. HER2 positivity rates show geographic variation (12.5–13.8% in Euro-Latin American cohorts) and higher prevalence in proximal tumors and chromosomal instability-high subtypes.

Aim:

The aim of this study was to assess HER2 expression via immunohistochemistry (IHC) in gastric carcinoma and correlate it with clinicopathological parameters and survival outcomes.

Materials and Methods:

Retrospective analysis of 55 histologically confirmed gastric carcinoma cases (2022–2025) at a tertiary care hospital. HER2 scoring followed Hofmann et al . criteria for gastric cancer. Associations used Chi-square, odds ratio (OR), and multivariate logistic regression; survival via Kaplan–Meier and Cox regression.

Results:

HER2 positivity (IHC 3+) occurred in 12.7% (7/55) cases, significantly linked to intestinal-type histology (OR 4.2, P = 0.02), higher grade ( P = 0.01), advanced stage ( P < 0.001), lymphovascular invasion ( P = 0.03), and lymph node metastasis ( P = 0.004). HER2-positive cases exhibited a median survival of 18 months versus 26 months for negatives ( P = 0.002, log-rank); HER2 remained an independent prognosticator (hazard ratio 2.8, 95% confidence interval 1.4–5.6, P = 0.003).

Conclusion:

HER2 overexpression portends aggressive behavior and inferior survival in gastric carcinoma, similar to findings in advanced cohorts with nodal metastasis (76.5%). Routine HER2 testing is imperative for prognostication and trastuzumab eligibility, despite resistance challenges.

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