Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Peripheriaki odos, Nea Efkarpia, 56403, Thessaloniki, Greece.
Strahlenther Onkol. 2013 Mar;189(3):202-14. doi: 10.1007/s00066-012-0275-0. Epub 2013 Feb 13.
EGFR (epidermal growth factor receptor), cyclin D1 and Akt/mTOR pathways are active in head and neck cancer. The aim of this study was to explore biomarker expression, their correlations with clinicopathological parameters and their prognostic utility in a cohort of patients with localized squamous laryngeal carcinoma.
We assessed relative messenger RNA expression of EGFR, Akt1, 2, and 3, mTOR and CCND1, copy number variants of the EGFR and CCND1 genes and immunohistochemical protein expression of EGFR, p-Akt308, p-Akt473, pmTOR, PTEN, p53 and cyclin D1 in paraffin-embedded tissue samples of localized laryngeal carcinomas.
In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumors of the larynx, high EGFR and CCND1 mRNA correlated with no or ex-smoking, (p = 0.003 and p = 0.029, respectively), while low Akt3 mRNA correlated with alcohol abuse, N0 stage, total laryngectomy, and absence of neck dissection. At a median follow-up of 74.5 months, high mTOR mRNA expression was marginally associated with shorter disease-free survival (hazard ratio [HR] = 1.54; p = 0.093) and high Akt3 mRNA with shorter overall survival (HR = 1.49; p = 0.0786), in univariate analysis. In multivariate analysis, node-positive status, subglottic-transglottic location, surgery other than total laryngectomy and mTOR/CCND1 mRNA interaction with a hazard ratio of 2.16 (p value for interaction: 0.0010) were independent predictors of relapse, while node-positive status and subglottic-transglottic location were associated with higher risk for death.
In localized laryngeal cancer, clinicopathological parameters and an interaction of high mTOR and CCND1 mRNA expression were found to be associated with poor patient outcome.
表皮生长因子受体（EGFR）、细胞周期蛋白 D1 和 Akt/mTOR 通路在头颈部癌症中活跃。本研究的目的是探讨生物标志物的表达及其与临床病理参数的相关性，并在局部鳞状喉癌患者队列中评估其预后价值。
我们评估了 EGFR、Akt1、2 和 3、mTOR 和 CCND1 的相对信使 RNA 表达、EGFR 和 CCND1 基因的拷贝数变异以及局部喉癌石蜡包埋组织样本中 EGFR、p-Akt308、p-Akt473、pmTOR、PTEN、p53 和 cyclin D1 的免疫组化蛋白表达。
在 289 名 T3-4（77.8%）、淋巴结阴性（84.1%）喉癌患者中，高 EGFR 和 CCND1 mRNA 与无或曾吸烟相关（p=0.003 和 p=0.029），而低 Akt3 mRNA 与酗酒、N0 期、全喉切除术和无颈清扫术相关。在中位随访 74.5 个月时，高 mTOR mRNA 表达与无疾病生存期较短（风险比[HR] =1.54；p=0.093）和总生存期较短相关（HR=1.49；p=0.0786），在单因素分析中。在多因素分析中，淋巴结阳性状态、声门下-跨声门位置、非全喉切除术和 mTOR/CCND1 mRNA 相互作用是复发的独立预测因素，风险比为 2.16（交互作用的 p 值： 0.0010），而淋巴结阳性状态和声门下-跨声门位置与死亡风险增加相关。
在局部喉癌中，临床病理参数和高 mTOR 和 CCND1 mRNA 表达的相互作用与患者预后不良相关。
