FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study

Background: In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials. Methods: FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed. Results: The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (Po0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P ¼ 0.0073) and UK (OS: 0.45 vs 1.9 years, Po0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P ¼ 0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour. Conclusion: A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive

Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas

Daoqiang Tang,1 Charles YJ Liu,2 Danping Shen,3 Shuqiong Fan,2 Xinying Su,2 Peng Ye,2 Paul R Gavine,2 Xiaolu Yin2 1Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 2Department of Translational Science, Asia and Emerging Market iMed, AstraZeneca R&D, 3Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China Aim: To investigate the significance of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER3 expression on survival outcomes in Chinese gastric cancer patients. Materials and methods: Formalin-fixed, paraffin-embedded specimens from 121 patients who underwent gastrectomy at Shanghai Renji Hospital from 2007–2010 were retrospectively examined. Fluorescence in situ hybridization and immunohistochemistry techniques were used to identify gene amplification and protein overexpression. Correlations between the expression or amplification of HER family genes and clinicopathological parameters were then determined using statistical analysis. Results: EGFR protein overexpression, an increase in HER2 copy number and gene amplification, and HER3 protein overexpression were identified in 33.1%, 17.4%, and 62.0% of samples, respectively. Statistical analysis showed a significant association between EGFR expression and tumor invasion depth or tumor stage. HER2 was also shown to be significantly associated with the tumor grade. In addition, EGFR protein overexpression was found to be significantly associated with worse overall survival (P=0.03). Conclusion: The HER family members showed a high expression in gastric cancer. EGFR protein expression was associated with overall survival. Keywords: gastric cancer, clinicopathologic significance, immunohistochemistry, fluorescence in situ hybridizatio