Abstract 12: c-MYC, EGFR, and FGFR2 expression and response and survival in neoadjuvant treated gastric cancer

Abstract

Abstract Introduction: Based on high-throughput transcriptional profiling and array comparative genomic hybridization, a three-gene predictor encompassing c-MYC, EGFR and FGFR2 has been identified to predict survival in cisplatin and fluorouracil (FU) – treated metastatic gastric cancer (GC) patients by others (1). The aim of our study was to determine the value of the expression of these three genes to predict response and/or survival for GC patients treated by a platin/5FU based chemotherapy in the neoadjuvant setting. Material and methods: Expression was analyzed in pretherapeutic tumor biopsies of 69 patients treated by platinum/5FU based neoadjuvant chemotherapy. Histopathological response was divided into three grades, tumor regression grade 1 (TRG1) corresponding to complete/major response, TRG2 corresponding to partial and TRG3 corresponding to minimal or no response. mRNA was isolated from manually microdissected formalin fixed and paraffin embedded tumor biopsies. Relative quantification of gene expression was performed by real time PCR using the delta-delta Ct method. As reference genes IPO8 and POLR2A were used and normalization was based on geometric averaging. Analyses were done in triplicates and the mean value was calculated. Fisher`s exact test or χ2-test (two sided) were used to test for an association with response. Overall survival was analyzed by log rank tests and Cox regression analyses. Results: Performing dichotomization of the patients based on median gene expression levels revealed a significant association of high c-MYC expression with minimal or no response (TRG3) (p=0.013). No other associations with response were observed for EGFR or FGFR2 expression in the study as a whole or in a separate analysis of patients with intestinal and nonintestinal type tumors. Testing various combinations of the expression of the three genes did not reveal a stronger association with response when compared to c-MYC expression alone. In the study as a whole, no statistically significant associations with overall survival were found. In the subgroup of nonintestinal-type tumors, univariate Cox regression analysis revealed a significantly increased risk of death for patients with a high expression of c-MYC (HR 59.56, 95%CI 1.28-2776.3; p=0.037). Conclusion: Our results indicate a prominent role of c-MYC expression to predict tumor shrinkage after platin/5FU-based neoadjuvant chemotherapy in GC and they suggest a prognostic relevance of this gene in particular for patients with nonintestinal-type gastric carcinomas. Reference: 1. Kim HK et al.: The Pharmacogenomics Journal (2012) 12: 119-127. Citation Format: Anna Munzig, Lukas Bauer, Julia Slotta-Huspenina, Alexander Novotny, Karen Becker, Alexander Hapfelmeier, Gisela Keller. c-MYC, EGFR, and FGFR2 expression and response and survival in neoadjuvant treated gastric cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 12.