HER2 status of gastric and gastroesophageal cancer (GC) patients assessed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and high-resolution array comparative genomic hybridization (aCGH).

Abstract

4103 Background: The ToGA study established the benefit of trastuzumab in HER2-positive GC. Accurate HER2 molecular assessment is crucial for patient selection for trastuzumab therapy. It is estimated by the ASCO/CAP that ∼20% of HER2 breast cancer (BC) testing is inaccurate. aCGH is a reliable, sensitive, and high-resolution method that characterizes gene copy number alternations present in tumors. aCGH is increasingly used as a research tool to help identify HER2-positive BC patients. Potential heterogeneity of HER2 amplification and incomplete membrane staining of HER2 by IHC leaves ambiguity of HER2 positivity in GC. We examined HER2 status by IHC, FISH, and aCGH in MSKCC GC patients with the aim to better define HER2-positive GC. Methods: Formalin-fixed paraffin-embedded (FFPE) tumor specimens of patients with GC were HER2 tested by FISH (PathVysion, Abbott-Vysis) and IHC (4B5, Ventana) at MSKCC and aCGH on Agilent 244K feature arrays at Cold Spring Harbor Laboratory. IHC and FISH results were scored according to the ASCO/CAP guidelines for BC. Age, gender, histology, stage, therapy, and survival were also recorded. Results: 100 patients with advanced GC have been studied. 22 women, 78 men. Median age 59. Median survival is 14 months, independent of HER2 status. aCGH analysis is ongoing; results are available on 22 patients (14 FISH positive, 5 FISH negative, 3 FISH equivocal), of which 1 IHC3+/FISH+ pt was found to be HER2 negative by aCGH. Conclusions: 21% of GC are HER2 FISH positive. FISH concordance rate is 100% for IHC positive and 94% for IHC negative. aCGH analysis is feasible on FFPE GC tumor specimens. We note a 93% concordance rate between FISH and aCGH positivity in GC thus far; additional analysis is ongoing. N=100 IHC0-1+ negative IHC2+equivocal IHC3+positive aCGH positive* log2 ratio >1.3 aCGH negative* Total FISH Positive >2.2 HER2:CEP17 1 3 16** 13 1 21* Negative <1.8 HER2:CEP17 66 3 0 5 71 Equivocal 1.8-2.2 HER2:CEP17 3 1 0 3 4 * Analysis is ongoing. ** 1 pt FISH+/IHC not available, 1 pt IHC 3+/FISH test failure. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GenDx, Inc. GenDX, Inc.