Human epidermal growth factor receptor-2 gene expression positivity determined by silver in situ hybridization/immunohistochemistry methods and associated factors in a cohort of Sri Lankan patients with gastric adenocarcinoma: a prospective study.

OBJECTIVE: Positive human epidermal growth factor 2 (HER2) expression and its predictive clinicopathological features remain unclear in Sri Lankan gastric cancer (GC) patients. Here, we aimed to determine GC HER2 status predictors by analyzing associations between clinicopathological features and HER2 expression using immunohistochemistry (IHC) and silver in situ hybridization (SISH). METHODS: During this 4-year prospective study, clinicopathological data were collected from participants in the National Hospital of Sri Lanka. HER2 IHC and SISH were performed using commercial reagents. Using chi-square tests, associations of HER2-IHC/SISH with clinicopathological features were analyzed. RESULTS: Overall, 145 GC patients were included, 69 had gastrectomies and 76 had biopsies. Positive HER2 expression by IHC was associated with age <60 years, high T stage (assessed pathologically in resections and radiologically in biopsies), high nuclear grade, tumor necrosis, mitosis >5/high-power field, with additional perineural invasion and lymphovascular invasion in resections. These features, excluding lymphovascular invasion but including male sex, were associated with HER2 expression by SISH. CONCLUSIONS: Age <60 years, high nuclear grade, tumor necrosis, and perineural invasion are associated factors of HER2 status. These could be used to triage GC patients for HER2 status testing in limited resource settings where IHC/SISH analysis is costly.

Human Epidermal Growth Factor Receptor-2 in Sri Lankan Gastric Carcinoma Patients with Clinicopathological Association and Survival.

BACKGROUND: HER2 protein expression indicates adverse prognosis in gastric adenocarcinoma (GCa). GCa HER2 positivity ranges from 10 to 22.8%. Similar data are scarce in South Asia and unavailable in Sri Lanka. AIM: To evaluate HER2 protein expression, its clinicopathological relationship and survival in a Sri Lankan GCa cohort. METHODS: One hundred consecutive GCa patients were recruited prospectively for 2 years. Histological diagnosis was confirmed on endoscopic biopsies/gastrectomy specimens. Clinicopathological and overall survival data were collected. HER2 expression was assessed using immunohistochemistry. 2+ and 3+ scores were considered positive. HER2 expression and clinicopathological parameters were analyzed by Chi-squared test and multivariate analysis with logistic regression using SPSS-21. Kaplan-Meier method and log-rank test were used for survival analysis. RESULTS: Study includes 56 biopsies and 44 resections. Male/female ratio was 1.9:1. Mean age of diagnosis was 61.1 years (range 32-82). Majority tumors were proximally located (58%). HER2 positivity was 9%. Even though intestinal subtype predominated HER2 positivity was mostly among diffuse variant (14.8%). In multivariate analysis, mitotic count >5/hpf, high nuclear grade and tumor necrosis were significantly associated with HER2 positivity, while poor differentiation, signet cells, extracellular mucin, perineural invasion and pathological nodal metastasis (all p < 0.05) showed a correlation in univariate analysis. Mean follow-up duration was 37.4 weeks (range 0-104). HER2 positivity was associated with a significantly lower median overall survival (p = 0.046). CONCLUSION: GCa HER2 positivity was 9%, associated with a lower median overall survival. Adverse histological features had a positive correlation with HER2 positivity. These histological features could direct patients for confirmatory HER2 testing in limited resource settings.