Ouyang Dai-Qiao, Liang Li-Zhong, Ke Zun-Fu, Zheng Guang-Sen, Weng De-Sheng, Yang Wei-Fa, Su Yu-Xiong, Liao Gui-Qing
Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Head Neck. 2017 Jun;39(6):1145-1154. doi: 10.1002/hed.24732. Epub 2017 Feb 23.
Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported.
P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data.
Expression of cytoplasmic and nuclear p-Akt, cytoplasmic p-mTOR, nuclear pan-Akt, and nuclear IGF-1Rβ were higher in ACC than in adjacent salivary glands. P-Akt, p-mTOR, PI3K, and IGF-1Rβ expression were correlated with one another in both cytoplasm and nucleus. Low p-mTOR expression in both subcellular compartments was associated with locoregional recurrence, poor disease-free survival (DFS), and overall survival (OS). Low nuclear p-Akt (Ser473) and p-mTOR expression were independent predictors for poor OS and DFS, respectively.
High level of Akt/mTOR activation in ACC is correlated with a significantly improved survival. P-mTOR and nuclear p-Akt are prognostic biomarkers of salivary gland ACC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1145-1154, 2017.
既往基因组研究显示,人类涎腺腺样囊性癌(ACC)存在磷脂酰肌醇-3激酶(PI3K)/Akt通路突变。尚未见对其预后价值进行验证的报道。
采用免疫组织化学方法检测120对涎腺ACC/癌旁涎腺组织中磷酸化Akt(P-Akt)、总Akt、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、PI3K和胰岛素样生长因子-1受体β(IGF-1Rβ),并与临床病理资料进行相关性分析。
ACC组织中细胞质和细胞核P-Akt、细胞质p-mTOR、细胞核总Akt及细胞核IGF-1Rβ的表达均高于癌旁涎腺组织。P-Akt、p-mTOR、PI3K和IGF-1Rβ在细胞质和细胞核中的表达均相互相关。两个亚细胞区室中p-mTOR低表达与局部区域复发、无病生存期(DFS)和总生存期(OS)较差相关。细胞核P-Akt(Ser473)低表达和p-mTOR低表达分别是OS和DFS较差的独立预测因素。
ACC中Akt/mTOR高水平激活与生存率显著提高相关。p-mTOR和细胞核P-Akt是涎腺ACC的预后生物标志物。©2017威利期刊公司。《头颈外科》2017年第39卷:1145 - 1154页。