हेपेटोलॉजी और गैस्ट्रोइंटेस्टाइनल विकारों के जर्नल
खुला एक्सेस

अमूर्त

Human Epidermal Growth Factor Receptor-2(HER-2) Expression in Sri Lankan Gastric Adenocarcinoma Patients: Analysis of the Concordance of HER2 Expression and Survival Based on Silver In-Situ Hybridization (SISH)

Duminda Subasinghe, Nathan Acott, Pasyodun Koralage Buddhika Mahesh, Sivasuriya Sivaganesh, Ananthi Samarasinghe, Mariyan Priyanthi Kumarasinghe, Dharmabandhu Nandadeva Samarasekera, Menaka Dilani Samarwickrema Lokuhetty

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 Cohen’s 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: The 69 gastrostomies 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. Core tip-HER2 positive Gastric Carcinomas (GC) are usually associated with more aggressive. Aim of this study is to find out HER-2 positivity based on IHC and SISH in Sri Lankan Gastric adenocarcinomas which was not described previously.