Abstract 4732: Analysis of KRAS variant in a cohort of resected HPV negative HNSCC

Abstract

Abstract Background: A single nucleotide polymorphism in let-7 complementary site 6 (LCS-6) of the KRAS 3’UTR reduces KRAS inhibition by the let-7 family of miRNA. It is associated with increased risk and greater proliferation of NSCLC tumors, and poor outcomes in ovarian cancers. It is also associated with platinum resistance in head and neck squamous cell carcinoma (HNSCC). The excision repair cross-complementing group 1 enzyme (ERCC1) plays an important role in nucleotide excision repair and double strand break repair, also affecting platinum resistance. We measured ERCC1 expression and KRAS LCS-6 variant status as prognostic markers for HNSCC outcome in a series of p16 negative tumors. Methods: KRAS variant status was determined by PCR (MiraDx) from DNA extracted from 99 available cases of p16 negative HNSCC in the Fox Chase Cancer Center Biosample Repository. Pearson’s Chi-squared tests and Wilcoxon tests were used to compare patient/tumor characteristics, including ERCC1 (HPA029773, Sigma) expression which was analyzed previously, by KRAS variant status. Overall survival was examined using Kaplan-Meier curves with log-rank tests for significance, and Cox proportional hazards regressions controlling for stage, grade, and tumor site. Results: A set of 99 p16 negative tumors (1990-2002) were analyzed: 62% male, 92% white, 53% moderately differentiated, 29% poorly differentiated. 72% stage III/IV disease. Smoking status was: 32% current, 15% never, 32% past smoker. Primary site of disease: 13% glottis, 44% oral cavity, 14% oropharynx, 20% oral tongue. The KRAS variant was identified in 27/99 (27%) of tissue samples, and in 21/62 (33%) of male patients versus 6/37 (16%) of female patients (P=0.06). Comparing by histologic grade the KRAS-variant was identified in 2/11 (18%) well differentiated tumors, 15/37 (40%) moderately differentiated and 9/29 (31%) poorly differentiated tumors (P=0.81). On univariate analysis, there was a non-significant increase in OS among all KRAS-variant patients (p=0.09) and those treated with surgery and adjuvant radiation (p=0.08). On multivariate analysis, the direction of the effect was maintained (all patients: HR=0.65, P=0.23; radiation subgroup: HR=0.41, P=0.06). There was no association between KRAS variant and ERCC 1 expression analyzed as a continuous variable (p = 0.70). Conclusions: In this small series, there was no association between the KRAS-variant and ERCC1 expression. Trends suggesting improved outcomes among KRAS-variant HPV negative patients treated with adjuvant radiation warrant further study. Citation Format: Jeffrey Mufson, Elizabeth Handorf, Joanne Weidhaas, Miriam Lango, Barbara Burtness, Erica Golemis, John A. Ridge, Ranee Mehra. Analysis of KRAS variant in a cohort of resected HPV negative HNSCC [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 4732. doi:10.1158/1538-7445.AM2017-4732