Human epidermal growth factor receptor 2 (HER2) positivity shown by fluorescence in-situ hybridization in patients with advanced gastric cancer: A multicenter study in Taiwan.

Abstract

e14576 Background: Based on the results of ToGA (Trastuzumab for Gastric Cancer) study, trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) cancer (Lancet 2010;376:687-97). In ToGA study, overall HER2-positivity rate was 22.1%; however, exceptionally low HER2-positivity rate was observed in some countries, including Taiwan (only 3%; ASCO-GI 2008:A11). The underlying factors contributing to low HER2-positivity rate in Taiwan remain obscured. Re-evaluation of HER2-positivity for Taiwanese GC patients in a larger sample size is highly warranted. Methods: We tested HER2-positivity by gene amplification using fluorescence in-situ hybridization (FISH) in formalin-fixed paraffin-embedded gastric or GEJ cancer samples. The testing was centralized to a single laboratory (Quest, UK). The PathVysion HER2 DNA probe Kit (Vysis, Abbott Molecular Inc., Germany) was used, which is FDA approved to detect the HER2 gene amplification. Results of hybridization on enumeration of 20 interphase nuclei from tumor cells are reported as the ratio of average HER2 copy number to that of CEP17, a specific region of the Chromosome 17’s centromere. Specimens with amplification showed a HER2 and CEP17 signal ratio of >/= 2.0. If the final ratio is calculated by the primary observer as near/at the cut-off point (1.8-2.2), an additional 20 cells is counted. The second observer will count an additional 20 cells. Results: Between Sep. 2007 and Nov. 2010, 180 patients (M:109, F:71) with gastric or GEJ adenocarcinoma from 8 medical centers in Taiwan were enrolled and evaluated by FISH testing. Among them, 47 patients (M:34, F:13) showed a HER2/CEP17 signal ratio of >/= 2.0, the overall HER2-positivity for Taiwanese GC patients was 26.1% (19.7%-32.5%, 95% CI). Conclusions: More than a quarter of Taiwanese advanced GC patients showed HER2-positivity by FISH, comparable with that of ToGA study. Novel HER2-targeted agents are justified for future active investigation in Taiwanese GC patients.