Human Epidermal Growth Factor Receptor-2(HER-2) expression in Sri Lankan gastric adenocarcinoma patients: An analysis of the concordance of HER2 expression and survival based on silver in-situ hybridization (SISH)

Abstract Background: Accurate HER2 status is crucial for gastric adenocarcinoma (GC) patient selection for antiHER2 therapy. It is assessed immunohistochemically (IHC) for protein expression, and by silver in-situ hybridization (SISH) for gene copy number. This study aimed to evaluate the concordance of HER2 status by IHC/SISH analyses and HER2-SISH based survival.Methods: This prospective study includes 145 GC’s (excluding gastro-oesophageal-junction tumours) from the National Hospital of Sri Lanka with defined demographic, clinical-radiological-pathological characteristics. HER2-IHC was assessed by DAKO A0485, RealTM Envision system and interpreted using Ruschoff criteria. HER2-SISH was assessed with INFORM HER2 dual ISH DNA Probe Cocktail. Concordance between HER2 IHC/SISH results was determined by Cohens kappa statistics. The association between the survival and HER2-SISH positivity was evaluated using the cox-regression method. Adjustments were done for age, gender, Lauren classification, tumour location and the tumour staging.Results: Of the 69 gastrectomies and 76 biopsies, 8.3% (n = 12) were HER2-IHC positive (n = 7, + 2 and n = 5, + 3). HER2-SISH positivity was 4.8 % (n = 7). All IHC + 3 were SISH positive, while two + 2 cases were SISH positive. Concordance for IHC 0, + 1, +3 were 100%. There was a significant overall correlation (kappa = 0.72, p < 0.001) between HER2-IHC and HER2-SISH indicating substantial concordance. The mean overall survival of HER2-SISH negative and positive patients were 41.7 (0-210) and 14.6 (3–51) weeks respectively, after a mean duration of patient follow up for 40.4 weeks (range 0-210). Survival was relatively lower (p = 0.001) in the group with HER2-SISH positivity.Conclusion: HER2-IHC was well concordant with HER2-SISH for 0, + 1, +3 scores and could be used for treatment and prognostication in low resource settings, where SISH facility is unavailable. HER2-IHC + 2, without gene amplification may be due to transcriptional activation by other genes or post-transcriptional events, mandating further evaluation by SISH. Survival of GC patients is significantly affected by HER2-SISH positive status.