Clinicopathological spectrum and HER2/MSI biomarker status in gastric adenocarcinoma: A tertiary care retrospective cohort from Pakistan.

Abstract

e16084 Background: Gastric cancer (GC) is a leading cause of cancer mortality in Pakistan, where delayed diagnosis, limited endoscopic access, and fragmented referral systems result in mostly advanced-stage presentations. Data on histopathological subtypes and actionable biomarkers, particularly HER2 overexpression and mismatch repair (MMR) deficiency, remain scarce. Understanding these patterns is crucial for guiding targeted therapies in tertiary care centers managing complex cases. Objective: To describe the clinicopathological spectrum and determine the prevalence of HER2 overexpression and MMR deficiency in gastric adenocarcinoma, with implications for personalized treatment strategies in Pakistan. Methods: We retrospectively reviewed 82 patients with primary gastric adenocarcinoma diagnosed between 2019 and 2024. Patients with prior chemotherapy, incomplete pathology, or non-adenocarcinoma histology were excluded. Tumors were classified according to WHO 2020 criteria. HER2 immunohistochemistry (IHC) was interpreted by two independent pathologists; equivocal cases were confirmed by FISH. MMR protein expression (MLH1, PMS2, MSH2, MSH6) was assessed to identify MSI-high tumors. Descriptive statistics summarized clinical and pathological features. Associations between categorical variables were analyzed using chi-square or Fisher’s exact tests, with p < 0.05 considered significant. Ethical approval was obtained (IRB-2023-0750). Results: The cohort (n = 82) had a median age of 58 years (IQR 50–65) and a male-to-female ratio of 1.6:1. The pyloric antrum was the most common tumor site (73.2%). Tubular adenocarcinoma predominated (75.6%), followed by signet ring cell carcinoma (SRCC, 12.2%). Most patients presented with advanced disease (stage III: 41.5%, stage IV: 26.8%). HER2 overexpression was observed in 14.6% (12/82), while MMR deficiency occurred in 8.5% (7/82). SRCC showed a significant inverse association with HER2 positivity (p = 0.02). All dMMR tumors were intestinal type. No associations were found between biomarkers and age or stage. Conclusions: Gastric adenocarcinoma in this Pakistani cohort predominantly affects the distal stomach and presents at advanced stages. HER2 overexpression and MMR deficiency occur at rates comparable to global reports, supporting biomarker-guided personalized therapy. Routine HER2 and MMR testing in tertiary centers is feasible and can inform targeted treatment strategies.