Prevalence of HER2 overexpression in gastric adenocarcinoma and its clinicopathological correlation: a prospective study from Bir Hospital, Nepal

Background: Gastric adenocarcinoma remains a leading cause of cancer-related mortality in Nepal. Trastuzumab, in the ToGA trial, has been shown to improve overall survival in HER2-overexpressing patients, with overexpression observed in approximately 22.1%. However, population-level data on HER2 status in Nepalese patients are conspicuously lacking, hindering informed clinical decision-making. Methods: This prospective observational study was conducted at Bir Hospital, Kathmandu, from January 2025 to January 2026. Fifty-eight patients with histologically confirmed gastric adenocarcinoma, including Siewert type III gastroesophageal junction (GEJ) tumors, were enrolled consecutively. HER2 expression was assessed by immunohistochemistry (IHC). An IHC score of 3+ was classified as positive; scores of 0, 1+, and 2+ were designated as negative. Fluorescence in situ hybridization testing was not performed for IHC 2+ cases due to resource constraints. Clinicopathological associations were analyzed using SPSS version 26, with significance set at P < 0.05. Results: The cohort comprised 58 patients (mean age 61.2 ± 12.54 years; range 25–86), with a male predominance of 70.7%. Tumors were predominantly antro-pyloric (62.1%), poorly differentiated (67.2%), and locally advanced (T3/T4 in 91.4%; stage III/IV in 81.0%). HER2 overexpression (IHC 3+) was detected in six patients (10.3%). A statistically significant association was observed between HER2 positivity and advanced T stage ( P -value < 0.05), with rates rising progressively from 0% in T2 to 30.8% in T4b tumors. Non-significant patterns favoring HER2 positivity were observed for proximal/GEJ location and male sex. No significant associations were identified with age, BMI, histological grade, distant metastasis, or overall disease stage (all P -values > 0.05). Conclusions: HER2 positivity (10.3%) in this Nepalese single-center series is lower than globally reported rates, likely reflecting the predominance of distal, poorly differentiated tumors in this cohort. Multicenter, larger-scale studies are warranted to validate these findings and refine HER2’s prognostic and predictive role in the Nepalese population.