Concordance Of Her2 Expression And Survival Based On Silver In-Situ Hybridization(Sish) In Gastric Adenocarcinoma

IntroductionGastric adenocarcinoma(GC) patient selection for antiHER2 therapy is dependent on accurate HER2 status. 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.MethodsThis prospective study includes 145 GC’s(excluding gastro-oesophageal-junction tumours) from the National Hospital of Sri Lanka. 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. SISH based survival of GC patients who did not receive antiHER2 therapy, was analyzed by Kaplan-Meier method and log-rank test.ResultsOf 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 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. The mean duration of follow up was 40.4 weeks (range 0–210). Survival was significantly poor(p=0.018) with HER2-SISH positivity.ConclusionsHER2-IHC was well concordant with HER2-SISH for 0, +1, +3 scores and could be used for treatment and prognostication in low resource settings. 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.