Cyclin D1, EGFR, and Akt/mTOR pathway
Cyclin D1, EGFR, and Akt/mTOR pathway
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DOI：
10.1007/s00066-012-0275-0
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发表时间：
2013-03-01
影响因子：
3.1
通讯作者：
Fountzilas, G.
中科院分区：
文献类型：
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作者：
Dionysopoulos, D.;Pavlakis, K.;Fountzilas, G.
表皮生长因子受体(EGFR)、细胞周期蛋白D1和Akt/mTOR信号通路在头颈癌中非常活跃。本研究旨在探讨局限性喉癌石蜡包埋组织中EGFR、Akt1、2、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EGFR、p-Akt308、p-Akt473、pmTOR、PTEN、P53和Cyclin D1的免疫组织化学表达，以及pmTOR、PTEN、P53和Cyclin D1的免疫组织化学表达。在289例T3~4(77.8%)、淋巴结阴性(84.1%)的喉癌组织中，EGFR和CCND1mRNA的高表达与不吸烟或戒烟有关(p=0.003和p=0.029)，而AKT3mRNA的低表达与酗酒、N0分期、全喉切除和未行颈淋巴清扫术相关。单因素分析显示，在74.5月的中位随访期中，mTOR mRNA高表达与较短的无病生存期(风险比[HR]=1.54；p=0.093)和高AKT3mRNA表达与较短的总生存期(HR=1.49；p=0.0786)略有关联。在多因素分析中，淋巴结阳性状态、声门下-跨声门区位置、除全喉切除以外的手术以及mTOR/CCND1mRNA相互作用(风险比为2.16p值：0.0010)是复发的独立预测因素，而淋巴结阳性状态和声门下-跨声门区位置与死亡风险相关。在局限性喉癌中，临床病理参数、mTOR和CCND1mRNA高表达的交互作用与患者预后不良相关。
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.