High Concordance of HER2 Overexpression by Immunohistochemistry on Mucosal Biopsies and Resection in Gastric Adenocarcinoma

Abstract

Introduction: High expression of Human Epidermal growth factor Receptor 2 (HER2) is a predictive biomarker for the treatment of gastric carcinomas with targeted agents. Targeted therapy could improve the outcome of patients with gastric carcinoma overexpressing HER2. There is limited information on mucosal biopsies to characterise the HER2 expression status of a tumour. Aim: To study HER2 expression by Immunohistochemistry (IHC) in matched mucosal biopsies and surgical specimens in patients with gastric adenocarcinoma and to discover the level of concordance. Materials and Methods: This was a prospective observational study conducted in the Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India, for one year (1st July 2016 to 30th June 2017). The IHC for HER2 was performed on matched mucosal biopsies and corresponding gastrectomy specimens of 72 patients. The HER2 overexpression (HER2+) was defined by a score 3+ on IHC. The results were analysed using Statistical Package for the Social Sciences (SPSS) software and Chi-square test was done for statistical significance. Results: The overall HER2 positivity rate was 11.11% (8/72). The HER2 positive rates (score 3+) were 9.72% on biopsy (7/72) and 8.33% on resection (6/72). Five cases showed concordance of HER2 between mucosal biopsies and resection specimens, however the other three cases showed a discordance i.e., two mucosal biopsies showed HER2 positivity and one resection showed HER2 positivity. The concordance rate in this study was 95.83% between resection and mucosal biopsies. Among the eight HER2 positive cases, five cases showed good concordance. One case showed positive shift: HER2 score was 0 on the mucosal biopsy and HER2 score was 3+ on the resection. Two cases showed a negative shift: mucosal biopsy showed HER2 score 3+ and the resection HER2 score 0. All the three discordant cases had received Neoadjuvant Chemotherapy (NACT) and showed heterogeneous staining on the resection specimen. None of the five concordant cases had received NACT and three of the five resections showed heterogeneous staining pattern. Conclusion: To the best of the authors’ knowledge, this was the first study to compare HER2 expression in gastric adenocarcinoma in matched biopsies and the corresponding resections in India. There was concordance of HER2 expression in 69 cases and discordance in three. Differences between biopsy and resection HER2 expression could be explained by intra-tumoural heterogeneity and possibly by decreased HER2 expression after NACT. The HER2 analysis by IHC on both mucosal biopsy and resections could optimise the selection of trastuzumab-eligible patients in case of gastric adenocarcinoma.

Keywords

• heterogeneity
• matched biopsies
• targeted therapy