Quantitation of HER2/neu Expression in Primary Gastroesophageal Adenocarcinomas Using Conventional Light Microscopy and Quantitative Image Analysis

CONTEXT: Human epidermal growth factor receptor 2 (HER2/neu) is overexpressed in a proportion of gastroesophageal (GE) adenocarcinomas, and trastuzumab treatment results in significant improvement in overall survival in patients with HER2/neu-overexpressing GE tumors. Grading of HER2/neu expression in GE tumors and its clinical application is different from that of breast cancer. HER2/neu immunohistochemistry (IHC) image analysis (IA), widely used in breast cancer, has not been studied in GE tumors. OBJECTIVE: To evaluate the correlation between manual HER2/neu IHC scoring and HER2/neu IHC image analysis in GE adenocarcinomas with characterization of associated clinicopathologic features. DESIGN: Tumor grade, growth pattern, and stage were evaluated in 116 cases of primary GE adenocarcinoma biopsy and resection specimens. Using anti-HER2/neu antibody and the proposed HER2/neu scoring system for gastric cancer, HER2/neu IHC expression was recorded after manual scoring and automated IA interpretation. RESULTS: HER2/neu overexpression (IHC 3+) was detected in 19% (10 of 54) of gastric tumors, and overall correlation between manual HER2/neu IHC interpretation and IA interpretation was 78% (42 of 54). HER2/neu overexpression (IHC 3+) was detected in 26% (16 of 62) of GE junction tumors, and the overall correlation between manual HER2/neu IHC interpretation and IA interpretation was 84% (52 of 62). CONCLUSIONS: The HER2/neu IHC scoring system for GE adenocarcinomas differs from that of breast carcinoma. Automated IA, validated for scoring of HER2/neu IHC in breast cancer, has a low correlation between HER2/neu IHC 2+ and IHC 3+ cases scored by conventional light microscopy and cannot be reliably used in the interpretation of HER2/neu IHC expression in GE adenocarcinomas.