膀胱移行细胞癌组织TGF-β1和细胞周期调控因子表达及其意义的研究

Expression of TGF-β1 and correlated cell cycle regulators in bladder transitional cell carcinoma and their regulation on cell proliferation

目的:通过检测TGF-β1、p21WAF1/CIP1(简称p21)、Cyclin D1和Ki-67在膀胱移行细胞癌(transitional cell carcinoma,TCCs)组织中的表达,探讨TGF-β1在膀胱癌细胞周期调控中的作用及对细胞增殖的影响。方法:应用免疫组化SP法检测50例TCCs标本和10例正常膀胱黏膜组织中TGF-β1、p21、Cyc-lin D1和Ki-67的表达,分析与病理分级、临床分期、肿瘤数目、复发的关系及相关指标之间的相关性。结果:TGF-β1在TCCs组阳性表达率为58%,显著高于正常膀胱黏膜组(20%),且与分级、分期呈负相关;初发组TGF-β1和p21表达均高于复发组,P<0.001。p21表达与分级、分期呈负相关,P<0.005。Cyclin D1随分级、分期增高其表达有增强的趋势,但差异无统计学意义,P<0.05;复发组、多发组的表达显著高于初发组、单发组。Ki-67表达随分级、分期升高,呈正相关;复发组、多发组表达显著高于初发组、单发组。TGF-β1与p21的表达呈正相关,与Ki-67呈负相关。结论:TGF-β1在TCCs早期表达升高,诱导细胞周期负性调控因子p21的表达,从而抑制Cyclin D1-CDK4/6复合物的活性,以及肿瘤生长。随着膀胱癌的恶变演进,TGF-β1表达下降,其诱导p21表达的作用减弱,而Cyclin D1促进细胞周期进程及其增殖作用占优势。

OBJECTIVE： To investigate the role of TGF-β1 on cell cycle in bladder TCC and the expressions of TGF-β1, p21^WAF1/CIP1 , Cyclin D1 and Ki-67 in specimens of patients with blad der transitional cell carcinoma. METHODS： The expressions of TGF-β1, p21, Cyclin D1 and Ki-67 were examined in 50 cases of bladder transitional cell carcinoma and 10 normal bladder mucosas by means of immunohistochemical SP technique. The correlations between the expression results and tumor pathological grades, clinical stages and number of lessions were studied respectively. RESULTS： The positive rate of TGF-β1 in TCC patients （58%） was significantly higher than that in the normal mucosas （20%）, which decreased with the advance of tumor grade and tumor stage. The primary tumor group had a higher level expression of TGF-β1 than the recurrent tumor group,P〈0. 001. The expression of p21 had negative correlation with tumor grade and tumor stage, P〈0. 005. The expression level of Cyclin D1 elevated with the advance of tumor grade and tumor stage, but there was not statistical significance,P〈0. 05. The primary tumor group had a higher expression level of p21 than the recurrent tumor group. The Ki-67 expression was positively correlated with both the increased grade and stage. There were higher expression levels of Ki-67 in recurrent tumors and multiple tumors than in primary ones and solitary ones. There was a positive correlation between TGF-β1 and p21. TGF-β1 and Ki-67 had a negative correlation. CONCLUSIONS： TGF-β1 expression increases in the early stage. At the same time p21 expression goes up induced by TGF-I？I. Then the high expression level of p21 can inhibit the function of Cyclin D1-CDK4/6 complexes to inhibite tumor growth. In the late stage, TGF-β1 expression decreases and the induction of p21 also reduces. So Cyclin D1 will accelerate cell cycle more strongly and result in progression of tumor.