HER2 Heterogeneity in Gastroesophageal Cancer Detected by Testing Biopsy and Resection Specimens.

CONTEXT: - In advanced gastric, esophageal, and gastroesophageal junction adenocarcinomas (GE-GEJ-AC) that overexpress ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2), anti-HER2 monoclonal antibody therapy confers survival benefit. To select patients for treatment, HER2 expression and gene amplification are evaluated by immunohistochemistry (IHC) and in situ hybridization.

OBJECTIVE: - To determine whether GE-GEJ-AC tested for HER2 on biopsy specimens of a primary tumor show different IHC scores and/or HER2 amplification by in situ hybridization in matched resection specimens, potentially changing therapy eligibility.

DESIGN: - Immunohistochemistry and silver in situ hybridization were performed in biopsy and/or resection specimens from 100 patients. HER2 testing was performed in matched resection and biopsy specimens of 15 cases to determine whether GE-GEJ-AC with IHC scores of 0, 1+ , and 2+ in biopsy and resection specimens had different IHC and silver in situ hybridization results.

RESULTS: - The IHC 3+ cases showed HER2 amplification in 4 of 5 cases (80%), and IHC scores of 0, 1+ , and 2+ showed 3.5%, 14.3%, and 23.5% HER2 amplification by silver in situ hybridization. Among the 15 paired biopsy and resection specimens, 9 (60%) had at least pT2 stage GE-GEJ-AC with HER2 IHC scores of 0, 1+ , or 2+ in the biopsy, and 2 of those 9 cases (22%) had IHC 3+ and HER2 amplification by silver in situ hybridization on the resection specimen.

CONCLUSIONS: - Our data suggest that HER2 testing should be repeated on resection specimens of GE-GEJ-AC with HER2 IHC scores of negative (0 and 1+ ) or equivocal (2+ ) and in situ hybridization amplification negative biopsy specimen results to evaluate for HER2 heterogeneity when patients are being considered for anti-HER2 therapy.