Dishevelled2基因及其蛋白在透明细胞性肾细胞癌组织中的表达及其临床意义

目的探讨透明细胞性肾细胞癌（CCRCC）组织及其癌旁组织中Dishevelled2（DVL2）基因及其蛋白的表达情况及其临床意义。方法用半定量反转录一聚合酶链反应（RT—PCR）和荧光实时定量PCR方法检测22例CCRCC患者的原位肾癌组织及其配对癌旁组织DVL2基因表达情况，并检测了32例总样本中Ⅲ＋Ⅳ期与I＋Ⅱ期肾癌组织中DVL2基因的表达差异；应用免疫组织化学法回顾性研究22例CCRCC患者的原位肾癌组织及其配对癌旁组织中DVL2蛋白的表达情况，同时检测了10例无正常肾组织配对的CCRCC患者肿瘤组织。结果半定量RT—PCR结果表明，在22例CCRCC样本中，DVL2mRNA在17例（77．2％）CCRCC原发灶中的表达较其配对癌旁组织上调，其结果与实时荧光定量PCR结果基本一致（仁2．535，P=0．0197），实时荧光定量PCR结果显示，13例Ⅲ＋Ⅳ期CCRCC中8例（61．5％）肾癌组织DVL2mRNA表达高于I＋Ⅱ期。肾癌组织；免疫组织化学分析表明，DVL2蛋白定位于CCRCC细胞的胞膜及胞质，22例CCRCC中有18例（81．8％）癌组织表达强度高于癌旁组织，但32例CCRCC的DVL2蛋白表达在不同年龄、性别、肿瘤分期间差异均无统计学意义（Fisher精确概率法，均P〉0．05）。结论在mRNA及蛋白水平上，CCRCC中DVL2表达水平显著高于癌旁组织，并且Ⅲ＋Ⅳ期肿瘤患者原位癌组织中DVL2的表达量高于I＋Ⅱ期，提示DVL2可能是一个潜在的与CCRCC发生及转移相关的分子标志物。

Expression of Dishevelled 2 gene and protein in clear-cell renal cell carcinoma tissues and its clinical significance

Objective To explore the relationship of DVL2 expression and the development of (CCRCC) by comparing the changes of DVL2 mRNA and protein expression in CCRCC specimens and matched normal renal specimens and its clinical significance. Methods DVL2 mRNA expressions in 22 CCRCC tissues, the matched adjacent normal tissues, and 10 CCRCC tissues alone were examined by semiquantitative RT-PCR and fluorescence quantitative PCR (real-time RT-PCR). Meanwhile, the different expression of the CCRCC between TNM Stage Ⅲ + Ⅳ and Stage Ⅰ +Ⅱ was also examined. Furthermore,immunohistochemistry was employed to examine DVL2 protein expression in 22 CCRCC and the matched adjacent normal tissues, and the other 10 CCRCC tissuses without the matched tissues. Results The DVL2 mRNA expression levels in 17 CCRCC tissues were increased by semi-quantitative RT-PCR and by real time RT-PCR compared with that in corresponding adjacent normal tissues, with the difference being significantly different (t = 2.535, P =0.0197). The DVL2 expression of 8 in 13 Ⅲ + ⅣCCRCC was higher than Ⅰ +ⅡCCRCC. Immunohistochemical examination showed that the DVL2 protein was located in cytomembrane and cytoplasm. Moreover, the positive level of DVL2 protein in CCRCC tissues[81.8 % (18/22)]was significantly higher than those in the adjacent tissues. However the expression was not associated with patients' age, gender, TNM stages (Fisher exact frenquently, P >0.05). Conclusion The DVL2 expression in CCRCC is obviously higher than the corresponding normal tissues in the level of mRNA and protein. And the higher DVL2 expression might be closely associated with the development and progression of CCRCC in the level of mRNA, which may be a potential molecular marker of CCRCC development and metastasis mechanism.