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.