HER2 Testing in Gastroesophageal Cancer Paired Biopsy and Resection Specimens, A Multi- Institutional Immunohistochemistry and Fluorescence In-Situ Hybridization Correlation Study

Eligibility for treatment with trastuzumab (Herceptin) for metastatic gastroesophageal cancer (GE) requires demonstration of HER2 protein overexpression or HER2 gene amplification. However, in the US there are no guidelines for best practices of HER2 testing in GE. The goals of this multicenter study were to first evaluate whether the published 2007 ASCO/CAP guidelines established for breast cancer could be extrapolated to GE cancers; and second, to implement an inter-laboratory comparison of HER2 IHC and FISH performance in paired biopsy and tumor resection specimens. Fifty paired formalin-fixed paraffin-embedded (FFPE) biopsy and resection specimens of GE carcinomas were selected from the pathology archives of three institutions. HER2 FISH analysis was performed using the PathVysion DNA probe kit. Immunohistochemistry was performed on the Ventana Benchmark XT with Ventana’s Pathway anti- HER-2/neu (4B5) antibody. Scoring and interpretation of results were according to the ASCO/CAP guidelines for breast carcinoma. Two of the 50 paired cases, were excluded due to insufficient quantity of residual tumor in the biopsy specimen. 48 and 38 pairs were successfully evaluated by IHC and FISH, respectively. Overall, the agreement of the IHC and FISH scoring between institutions was good; Ƙ = 0.76 (IHC) and very good; Ƙ = 0.89 (FISH). The concordance between biopsies and resection specimens was 96% and 97% with IHC and FISH, respectively. We present data from an inter-laboratory collaborative study of the performance of HER2 IHC and FISH within GE tumors in paired biopsy and resection specimens. We found that the 2007 ASCO/CAP guidelines can be applied to GE cancer with good inter-observer reproducibility.