HER2 positive gastroesophageal cancer in an Irish population.

Abstract

e14687 Background: Gastroesophageal cancer is a major cause of cancer-related mortality. HER2 is overexpressed in ~ 7-34% of gastroesophageal (GE) adenocarcinomas. The ToGA study, established the benefit of trastuzumab in combination with chemotherapy in HER2 positive metastatic GE tumours. In this study, 22% of patients were HER2 positive {immunohistochemistry (IHC)3+ or fluorescence insitu hybridization (FISH)(+)}. Potential heterogeneity of HER2 amplification, overexpression, and incomplete membrane staining of HER2 by IHC leaves some ambiguity in HER2 testing and definition of HER2 positive GE tumours. We report a multi-center Irish experience by examining HER2 status by IHC and FISH in GE tumours. Methods: HER2 testing was performed on adenocarcinoma biopsy or resection specimens of patients with early stage and metastatic GE tumors between 2008 - 2011. We defined HER2 positive as IHC3+ or FISH(+) {HER2:17ch ≥ 2}. In addition, age, gender, smoking history, histology, stage of disease, treatment, and survival data were recorded. Results: A total of136 Caucasian patients with early stage and metastatic GE cancers were identified. Median age was 69 yrs (ranging from 25 – 96). Data available for analysis was conducted from 111 patients with 10% FISH(+). There are 73 patients with early stage and 38 with metastatic disease. Five metastatic cases (13%) were FISH(+) (of whom 3 IHC3+, 1 IHC2+, 1 IHC1+), 33 cases were FISH(-). Sites of metastatic disease in the FISH(+) cohort were liver, peritoneal, and bone metastasis. In the FISH(-) group, sites of metastatic disease were predominantly liver. Interestingly CNS disease is seen exclusively in the FISH(-) cohort. Of the early stage patients, only 6 patients (8.2%) were FISH(+) (of whom 3 IHC3+, 2 IHC2+, 1 IHC1+). With respect to tumour heterogeneity of HER2 amplification, in IHC3+, 82% were FISH(+), IHC2+, 17% were FISH(+) and IHC1+, 6% were FISH(+). There was 100% concordance between IHC0 and FISH(-). Conclusions: HER2 positive GE adenocarcinomas in the analyzed cohort displays similar pattern of heterogeneity in IHC staining and FISH positivity but with lower incidence (10%) of HER2 amplification than was reported in the ToGA study. Further data on location, histological pattern and survival will be reported.