膀胱移行细胞癌组织中聚集素、Ki-67蛋白表达和细胞凋亡的测定

目的 探讨聚集素在膀胱移行细胞癌组织中的表达及其与细胞增殖和凋亡的关系。方法制作87例膀胱移行细胞癌组织的组织芯片,分别应用免疫组织化学和末端脱氧核苷酸转移酶介导缺口末端标记方法,检测膀胱移行细胞癌组织中聚集素和Ki-67蛋白表达及细胞凋亡情况,分析聚集素蛋白表达与肿瘤分化、临床分期等病理特征及肿瘤细胞凋亡、增殖及Ki-67蛋白表达的关系。结果43％（37／87）患者为聚集素蛋白过度表达,且聚集素蛋白表达与肿瘤细胞的分化程度、肿瘤的浸润深度均有显著的相关性（r分别为14．1,10．2,P均〈0．01）;71％（20／28）低分化（G3）和62％（23／37）浸润型（T2-4期）患者的肿瘤组织聚集素蛋白过度表达,过度表达率明显高于分化较好（G1-2,29％,17／59）和浅表型（Ta-1期,28％,14／50）者。聚集素蛋白表达与肿瘤的凋亡指数（AI）呈负相关（r=7．31,P〈0．01）,但与Ki-67的表达水平无关;聚集素过度表达的肿瘤,57％（21／37）表现为低AI值（≤1．2％）,而聚集素正常表达的肿瘤,则72％（36／50）为高AI值。结论膀胱移行细胞癌组织中聚集素蛋白过度表达与肿瘤的分化程度和浸润深度呈正相关,与肿瘤细胞的AI呈负相关。

The detection of protein expression of clusterin and Ki-67 and the status of cell apoptosis in bladder transitional cell carcinoma

OBJECTIVE: To investigate the expression of clusterin protein in bladder transitional cell carcinoma (BTCC) and it's association with tumor cell proliferation and apoptosis. METHODS: A tissue microarray (TMA) containing 87 informative cases of BTCCs was constructed firstly. The methods of immunohistochemistry and terminal deoxynucleotidyl transferase-mediated nick end-labeling were then used to examine the expression of clusterin and Ki-67 protein and the status of cell apoptosis in BTCC, respectively, and the correlations between different markers and the clusterin expression associated with patients' clinico-pathological features were evaluated. RESULTS: In TMA of 87 BTCCs, 37 (43%) cases were observed overexpression of clusterin. A significant association of clusterin expression with BTCC's pathological grade, as well as with tumors clinical stage was observed (P < 0.01), where the frequency of overexpression of clusterin in poor differentiated BTCCs (G(3), 71%) and tumors in more advanced stage (T(2-4), 62%) was significantly higher than that in well differentiated BTCCs (G(1-2), 29%) and tumors in early stage (T(a-1), 28%). In addition, a significant correlation between clusterin expression and tumors apoptotic index (AI) was evaluated (P < 0.01), in which 57% of BTCCs with overexpression of clusterin were observed a lower AI, while 72% of tumors with normal expression of this protein showed a higher AI, but no correlation between clusterin and Ki-67 expression. CONCLUSIONS: The overexpression of clusterin is associated positively with BTCC's malignant clinical phenotypes including tumor's differentiation and invasive depth, and it is correlated inversely with AI of tumor cells.