Expression of HER2 in gastric cancer: Comparison between protein expression and gene amplification using a new commercial kit

Abstract

4053 Background: Trastuzumab, a monoclonal antibody to HER2 protein, is widely used in patients with HER2-overexpressing breast cancer. Trastuzumab has also shown antitumor activity in human gastric cancer (GC) xenograft models with HER2 overexpression, however, the concordance of protein expression and gene amplification of HER2 in GC cells and the feasibility of using biopsy specimens has not been clarified Aim: The purpose of this study was to evaluate the frequency of HER2 overexpression and the concordance between protein expression and gene amplification in surgical and endoscopic biopsy GC specimens using two commercial immunohistochemical(IHC) kits and fluorescence in situ hybridization (FISH). Materials and Methods: The specimens consisted of formalin-fixed, paraffin-embedded sections of biopsy specimens and surgically resected tumors in 200 cases with invasive GCs who underwent surgery at the National Cancer Center Hospital East. The IHC analysis was performed using the Hercep Test kit (DAKO Corp, Carpinteria, CA), and the expression grading was estimated using an FDA-approved grading system. HER2/neu gene amplification was evaluated using the PathVysion erb2 DNA probe kit (Vysis, Stuttgart-Fasanenhof, Germany). Results: Among these 200 cases, 46 (23%) of the patients were found to exhibit HER2 protein overexpression. The following IHC scores were obtained: 0,126(63%);1+, 28(14%);2+,12(6%);and 3+,34(17%). The FISH assay was technically successful in 199 cases (99.5%).Gene amplification was observed in 54 cases (27.1%). The concordance rate between IHC and FISH in the Her2-protein-overexpression cases was 86.7% (58.5% for 2+, 88.2% for 3+). Among the 200 biopsy specimens, Her2 protein overexpression was observed in 21.5% of the specimens (2+,7.5%; and 3+,14%). The concordance rate between the surgically resected materials and the biopsy specimens was 88.7%. Conclusion: HER2 expression can be assessed in GC tissue as previously reported for breast cancer tissue, using the with Hercep Test and Pathvysion. Furthermore, small biopsy specimens are suitable for evaluating Her2 overexpression in GC cells. No significant financial relationships to disclose.