Abstract

Abstract In previous study, we have evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease free survival (DFS) and observed that the percentage of residual viable tumor cells were associated with OS and DFS in 192 NSCLC patients receiving neoadjuvant chemotherapy. In current study, we examined the selected protein biomarkers by IHC in surgical specimens of 98 NSCLC patients receiving neoadjuvant chemotherapy. All NSCLC patients treated with neoadjuvant chemotherapy received a platinum and taxane-based. For IHC analysis of protein markers, we selected candidate biomarkers (VEGFR2, EZH2, ERCC1 and Rad51) on the basis of the literature. Next, the results of VEGFR2, EZH2, ERCC1 and Rad51 expression were analyzed with regard to pathologic response and overall survival time of the patients. The surgical pathologic stage, percentage of viable tumor cells and Rad51 were associated with OS in 98 NSCLC patients receiving neoadjuvant chemotherapy in univariate and multivariate analysis. We found that patients with high-level expression of Rad51 had a poorer prognosis than did those with low-level expression. We observed that Rad51 expression was associated with pathologic response (viable tumor cells). However, there is no association between VEGFR2, EZH2, or ERCC1 expression and pathologic response (viable tumor cells). We further examined K-Ras and EGFR Mutation in these NSCLC tumors receiving neoadjuvant chemotherapy. We analyzed the hotsport mutations in K-Ras gene (Codon 12 and 13) and EGFR gene (Exon 19 and 21) by pyrosequencing and confirmed by direct sequencing method in 98 NSCLC tumors receiving neoadjuvant chemotherapy. We observed both methods had similar results on these patients’ samples. The L858R mutation results in an amino acid substitution at position 858 in EGFR, from a leucine (L) to an arginine (R). This mutation occurs within exon 21, which encodes part of the kinase domain,We found K-Ras mutation tended to be associated with OS, but not EGFR mutation. There is no association between percentage of viable tumor cells, VEGFR2, EZH2, ERCC1, Rad51 expression and K-Ras or EGFR mutation. Citation Format: Apar Pataer, Ruping Shao, Arlene M. Correa, Carmen Behrens, Jack A. Roth, Ignacio I. Wistuba, Stephen G. Swisher. Evaulate biomarkers in NSCLC tumors receiving neoadjuvant chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1908. doi:10.1158/1538-7445.AM2015-1908

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