mTOR信号通路在Xp11.2易位/TFE3基因融合相关性肾癌中的表达及其意义

Expression and clinical significance of signal path of mTOR on renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion

目的:探讨mTOR信号通路在Xp11.2易位/TFE3基因融合相关性肾癌(简称TFE3肾细胞癌)中的表达及其意义。方法:选取TFE3肾细胞癌23例、肾透明细胞癌组织60例和乳头状肾细胞癌20例。采用免疫组化方法检测3种肾细胞癌组织中p-mTOR与P70S6K的表达情况,观察二者表达与3种肾细胞癌的关系,进而研究mTOR信号通路与TFE3肾细胞癌发生发展的关系。结果:p-mTOR在TFE3肾细胞癌、肾透明细胞癌和乳头状肾细胞癌中的表达分别为(83.7±3.2)、(49.5±6.7)和(46.8±5.3)(P<0.05)。P70S6K在TFE3肾细胞癌、乳头状肾细胞癌组和肾透明细胞癌中的表达分别为(88.2±9.8)、(42.7±6.7)和(52.4±7.1)(P<0.05)。p-mTOR在年龄<35岁组和年龄≥35岁组的TFE3肾细胞癌表达为(212.0±75.9)和(27.3±47.5),在有淋巴结转移组和无淋巴结转移组表达为(255.0±21.2)和(72.1±93.4),在有脉管瘤栓组和无脉管瘤栓组表达为(225.0±35.5)和(81.6±89.4),两组比较差异均有统计学意义(P<0.05)。P70S6K在年龄<35岁组和年龄≥35岁组的TFE3肾细胞癌组织中的表达为(220.0±63.2)和(30.3±49.7),在有淋巴结转移组和无淋巴结转移组表达为(187.0±47.5)和(45.1±73.6),在有脉管瘤栓组和无脉管瘤栓组表达为(240.0±42.4)和(73.5±95.9),两组比较差异均有统计学意义(P<0.05)。TFE3肾细胞癌组织中p-mTOR和P70S6K表达的H-score评分呈正相关(r=0.987,P<0.05)。结论:与肾透明细胞癌和乳头状肾细胞癌组织相比,TFE3肾细胞癌组织中pmTOR与P70S6K表达显著增高,有助于TFE3肾细胞癌的鉴别诊断。TFE3肾细胞癌中P70S6K和p-mTOR表达与患者年龄、脉管瘤栓和淋巴结转移等因素相关,而与肿瘤直径大小和性别无关。TFE3肾细胞癌中mTOR信号通路处于激活状态,为TFE3肾细胞癌的分子治疗提示潜在作用靶点。

Objective：To detect the expression of p-mTOR/P70 S6 Kon renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion（TFE3 RCC）and to explore its function and clinical significance on the occurence and development of this type of renal cell carcinoma（RCC）.Method：Twenty-three TFE3 RCC cases,60 cases of renal clear cell carcinoma（CCRCC）and 20 cases of papillary renal cell carcinoma（PRCC）were selected and performed with immunohistochemistry（EnVision method）to detect the expression of p-mTOR/P70 S6 K.We observed the correlation between the expressions and three types of RCC and the relationship between the expressions and the genesis and development of TFE3 RCC.Result：The expression level of p-mTOR/P70 S6 Kin TFE3 RCC tissue was markedly higher than that in CCRCC and PRCC tissue.It showed p-mTOR：[（83.7±3.2）vs.（49.5±6.7）,（83.7±3.2）vs.（46.8±5.3）,P0.05];P70 S6 K：[（88.2±9.8）vs.（52.4±7.1）,（88.2±9.8）vs.（42.7±6.7）P0.05].The expression of p-mTOR/P70 S6 Kin TFE3 RCC tissue was evidently correlated with patients＇ age,lymph node metastasis,carcinoma cell embolus.It showed p-mTOR：[（212.0±75.9）vs.（27.3±47.5）,（255.0±21.2）vs.（72.1±93.4）,（225.0±35.5）vs.（81.6±89.4）,P0.05];P70 S6 K：[（220.0±63.2）vs.（30.3±49.7）,（187.0±47.5）vs.（45.1±73.6）,（240.0±42.4）vs.（73.5±95.9）,P0.05].But no association between the expression of p-mTOR/P70 S6 Kin TFE3 RCC tissue and the diameter or gender was found.There was a positive correlation between p-mTOR and P70 S6 Kexpression in TEF3 RCC（r=0.987,P0.05）.Conclusion：Compared with CCRCC and PRCC,the expression of p-mTOR/P70 S6 Kin TFE3 RCC tissue increased significantly,which could help the differential diagnosis of TFE3 RCC.The expression of pmTOR/P70 S6 Kin TFE3 RCC tissue was evidently correlated with patients＇ age,lymph node metastasis,carcinoma cell embolus,but not associated with the diameter and gender.The signal path of mTOR in TFE3 RCC was activated specifically,which could be the potential drug target for the TFE3 RCC.