【作者】 艾宁； 田建华； 李铭； 倪晓辰； 陈亮； 徐芝立；

【Author】 Ai Ning Tian Jian-Hua Li Ming Ni Xiao-Chen Chen Liang Xu Zhi-Li Department of Urology The fourth hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院泌尿外科；

【摘要】 目的:目前普遍认为肾癌的发生发展是一个多基因、多阶段的过程,其发生机制十分复杂,研究表明许多癌基因的激活及抑癌基因的失活参与了这一过程。PTEN为新近发现的具有磷酸酶活性的肿瘤抑制基因,有参与胚胎正常发育,诱导细胞凋亡,抑制细胞迁移,铺展和局部粘附功能。拟探讨抑癌基因PTEN、p27kipl蛋白在人肾细胞癌中的表达定位和表达水平,及两种抑癌基因蛋白表达的相关性。方法:应用免疫组织化学S—P法,检测43例肾癌组织、18例癌旁非癌肾组织及 5例非瘤正常肾组织中PTEN、p27kipl蛋白的表达情况,将表达结果与组织学类型、组织学分级、淋巴转移、临床分期和临床预后等生物学行为进行相关分析。结果:1 PTEN蛋白主要表达在细胞浆,细胞核有少量表达,正常肾组织细胞中 PTEN蛋白表达全部为阳性,肾癌癌旁非癌肾组织PTEN蛋白阳性高表达率为94．4％(17／18),肾癌组织中阳性高表达率为 65．1％(28／43),差异具有统计学意义(p<0．05)。PTEN蛋白与淋巴结状态、临床分期及远处转移有关。2 p27kipl主要在细胞核表达,正常肾组织中p27kipl表达均为阳性,癌旁非癌肾组织p27蛋白高表达率为88．9％(16／18),明显高于肾癌组织中阳性高表达率53．5％(25／43),差异具有统计学意义(p <0．01)。p27kipl蛋白与淋巴结状态、肿瘤大小、临床分期及远处转移有关。3 PTEN蛋白与p27kipl蛋白呈明显的正相关 (r=0．394 p<0．01)。4随访到37例患者,其中10例患者在术后5年内因肿瘤死亡,7例术后有远处转移。经检验,死亡组病例、远处转移组病例及无瘤生存组病例PTEN蛋白表达组间有显著性差异(x2=7．549 P=0．023<0．05),同时p27kipl 蛋白表达组间也有显著性差异(x2=9．326 P=0．009<0．01)。结论:1 PTEN蛋白在正常肾组织中呈强阳性表达,在肾癌组织中表达减低,提示它可能在肾癌的发生发展中起重要作用,PTEN的表达与肾癌的组织学类型无关,与肾癌的病理分级及临床分期和淋巴结转移密切相关,可作为判断肿瘤浸润进展的指标。2 p27kipl蛋白表达强度与肾癌的临床分期与病理学分级密切相关,分期越差,表达强度越弱,这也在一定程度上反映了肾癌的进展与预后。3 PTEN通过上调p27伴随下调cyclinD1协调对细胞周期G1的阻滞,PTEN与p27表达呈正相关的关系,p27可能是PTEN的下游基因。4 PTEN、 p27kipl蛋白阳性表达的肾癌患者预后显著好于PTEN、p27kipl 蛋白阴性表达的肾癌患者,因此检测肾癌组织中的PTEN、 p27kipl蛋白表达可作为估计病情发展、判断患者预后的重要指标。更多还原

【Abstract】 Objective: It’s widely recognized that on-cogenesis of kidney carcinoma is a multigene, multistage process. A lot of reports have showed that activation of oncogenes and inactivation of tumor suppressor genes are involved in renal carcinoma. PTEN is a tumor suppressor gene with phosphatase activity, has complexful functions including participating in the embryonic growth, apoptosis and G1 phase cell block, inhibiting the migration and adherence.To investigate the expression of PTEN gene in human renal cell carcinoma (RCC) and the correlation between the expression of PTEN and the expression of P27kipl. Methods: The PTEN protein of 43 cases of RCC tissues confirmed by pathology after operation, 18 cases of adjacent normal renal tissues, and 5 cases of non-tumor normal renal tissues were assessed using immunohis-tochemistry SP method. PTEN protein expression was compared with clinical pathologic parameters as related to p27kipl. Results: 1 PTEN showed cytoplasm staining. Normal renal tissues were all positive for PTEN protein. In the corresponding paratumor tissues, 94.4% were positive for PTEN. In the tissues from RCC, it was 65.1 % positive for PTEN protein. It was statistically different (p< 0.05). PTEN expression level was correlated with lymph node status and metastasis. Overexpression of p27kipl immunostaining was mostly in nuclear, and sometimes it showed cytoplasm staining in the renal cell carcinoma. The researches had showed that normal renal tissues were all positive for p27kipl protein. In the corresponding paratumor tissues, 88.9% of them were positive for p27kipl. But in the tissues from RCC,the positive rate was declined to 53.5% for p27kipl protein, so it was statistically different (p<0. 01). PTEN expression level was correlated with lymph node status, tumor size and metastasis. 3 Between the expression of PTEN and p27kipl showed significantly positive cor-relation( r=0.394 p<0.01 ). 4 With the prognosis of 37 cases, 10 cases showed death and 7 cases showed metastasis in 5 years. It was significantly different in the groups which was made with the prognosis result (PTEN x 2=7.549 p= 0.023<0.05; p27kipl x 2=9.326 p=0.009<0.01). Conclusion: The expressions of PTEN were highly positive in normal renal tissues, but those were low in renal carcinoma. It shows that PTEN may play important roles in renal carcinoma generation and development; the expressions of PTEN were not related to pathological types ,but closely related to clinical stage, pathological grade and lymps nodes metastasis.It clould be a marker of development evaluation. There is relationship between p27 expression and Robson stage.It shows the correlation between low-grade expression of p27 and the oncogenesis, progression and prognosis of RCC.The expression of p27 protein is a reliable marker for determining its prognosis. PTEN passed up-regulation p27 and down-regulation cyclinD1 to blockage cell cycle G1, inhibiting growth, differentiation and lymph node metas更多还原