Abstract

Abstract Gallbladder carcinomas involve multiple cascades of oncogenes like EGFR and Kras. Activation of Kras downstream pathways predict the sensitivity to anti EGFR treatment. In 2012, for the first time it was established that GBC and cholangiocarcinomas have their unique somatic genomic landscape and thus be studied independently. This study evaluates whether EGFR is a prognostic factor in GBC and identifies the frequency of codon 12 and codon 13 Kras mutations along with its association with subject survival. Seventy two GBC curative resections from North India were immunostained with anti EGFR monoclonal antibody and assessed for codon 12 and 13 KRAS mutation by real time PCR. Strong EGFR expression was observed in 25.4percent cases. About 28/72; G12C, 17/72; G12R, 10/72; G12D and 18/72; G13D cases harboured point mutations in Kras gene, which was significantly higher as compared to control tissues. Multivariate analysis revealed that EGFR expression (p=0.01; HR=3.14; 95percent CI=1.28-7.71) and codon-13 mutation (p=0.001; HR=38.34; 95percent CI=4.90-300.01) had a significant impact on survival and were independent prognostic factors in GBC. Our study suggests that EGFR expression and codon 13 mutations are independent prognostic factors in the selected GBC cohort and showed a high frequency of Kras codon 12 mutations as well. Citation Format: Anjali Singh, Abul Kalam Najmi, Pramod Mishra, Majid Talikoti. Prognostic importance of EGFR expression and Kras gene mutations in gallbladder carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 671. doi:10.1158/1538-7445.AM2017-671

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