谷胱甘肽转硫酶-Pi与缺氧诱导因子-1α在膀胱癌组织中的表达及其意义

Expression and Significance of GST-Pi and HIF-1αin Bladder Carcinoma

背景与目的:多药耐药在膀胱癌化疗失败中起着重要作用,关于其机制还不是十分清楚。缺氧诱导因子(hypoxia-induciblefactor,HIF-1α)是调节肿瘤组织适应缺氧的核转录因子,关于其与膀胱癌多药耐药转录蛋白的研究还鲜见报道。本研究利用组织微阵列研究谷胱甘肽转硫酶-Pi(GST-Pi)和HIF-1α在膀胱癌组织中的表达、相互关系及临床意义。方法:构建膀胱癌组织微阵列,利用免疫组织化学SABC法检测119例膀胱癌中GST-Pi、HIF-1α的表达。设7例膀胱正常组织作对照。结果:GST-Pi总阳性表达率67.2%,HIF-1α总阳性表达率57.9%,特别是在G3级HIF-1α表达率为64.6%。二者的表达与膀胱癌病理分级、临床分期和术后膀胱腔内化疗的复发率密切相关。而且发现GST-Pi与HIF-1α协同表达,GST-Pi表达高者,HIF-1α表达也高,且膀胱癌的分级分期也高。结论:HIF-1α在膀胱癌中高表达可能与缺氧有关,HIF-1α和GST-Pi协同表达是判定膀胱癌恶性程度及多药耐药程度的客观指标。

BACKGROUND ＆ OBJECTIVE： Multidrug resistance plays an important role in chemotherapy failure of bladder cancer, but its mechanism is unclear. Hypoxia in tumors is generally associated with chemoresistance. However, the correlation of nuclear transcription factor hypoxia-inducible factor-1 （HIF-1） to multidrug resistance transporter glutathione-S-transferase- Pi （GST-Pi） has not been investigated. This study was to explore the expression and significance of GST-Pi and its correlation to HIF-1α in bladder carcinoma by tissue microarray. METHODS： A tissue microarray containing 119 cases of bladder carcinoma and 6 cases of normal bladder tissue was built up. The expression of GST-Pi and HIF-1α was detected by SABC immunohistochemistry. RESULTS. in the 119 cases of bladder carcinoma, the positive rate of HIF-1α was 57.9%, the positive rate of GST- Pi was 67,2%. The positive rate of HIF-1α in G3 grade bladder carcinoma was 64.6%. Their expression was closely related to pathologic grade, clinical stage, and postoperative relapse after adjuvant chemotherapy （P〈0.01）. HIF-1α expression was positively related to GST-Pi expression （P〈0.01）. CONCLUSIONS： Overexpression of HIF-1α may be related to hypoxia. Coexpression of HIF-1α and GST-Pi is a object index for judging differentiation and chemoresistance of bladder cancer.