1031P - Cyclin D1, EGFR and AKT/MTOR Signalling in Localized Laryngeal Squamous Cell Carcinoma

Abstract

ABSTRACT Introduction EGFR pathway, Akt/mTOR and Cyclin D1 are activated and interact in squamous cell head and neck cancer. Patients and methods We assessed relative mRNA expression of EGFR, Akt1, 2, 3, mTOR and cyclin D1, copy number variants of EGFR and CCND1 genes and immunohistochemical (IHC) expression of EGFR, pAKT308, pAKT473, pmTOR, PTEN, p53 and cyclin D1 in paraffin-embedded tissue of localized laryngeal carcinomas. Results In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumours of the larynx, high EGFR and CCND1 mRNA correlated with never or ex smoking, (p = 0.003) and (p = 0.029) respectively, while low AKT3 correlated with alcohol abuse. At a median follow-up of 74.5 months, high mTOR RNA was marginally associated with shorter DFS, HR = 1.54, p = 0.093 and high Akt3 mRNA with shorter OS, HR = 1.49, p = 0.0786 whereas high EGFR IHC expression was associated with shorter DFS HR = 1.60, p = 0.0311 and OS HR = 1.57, p = 0.056, pAKT308 with shorter OS, HR = 1.003, p = 0.0586 and pAKT473 with shorter DFS HR = 1.004, p = 0.021 and OS HR = 1.004, p = 0.033, all in univariate analysis. An interaction between mRNA levels of mTOR and cyclin D1 was found to be associated with shorter DFS, namely at high mTOR mRNA expression, one unit increase of CCND1 mRNA expression had aHR = 2.16 and this remained statistically significant in multivariate analysis (p-value for interaction = 0.0010). In multivariate analysis, node-positive status, subglottic-transglottic localization, surgery other than total laryngectomy and mTOR/cyclin D1 mRNA interaction, were independent predictors of relapse, while node-positive status, and subglottic-transglottic localization were associated with higher risk of death. Conclusions In laryngeal cancer, an interaction of high mTOR and cyclin D1 mRNA expression is associated with poor patient outcome. Disclosure All authors have declared no conflicts of interest.