Pertia Ambrosi, Nikoleishvili David, Trsintsadze Omar, Gogokhia Nino, Managadze Laurent, Chkhotua Archil
Departments of Adult Urology, National Centre of Urology, Tsinandali st 9, 0144, Tbilisi, Georgia.
Int Urol Nephrol. 2007;39(2):381-7. doi: 10.1007/s11255-006-9077-6. Epub 2007 Feb 20.
The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27((Kip1))CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27((Kip1)) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27((Kip1)) expression in RCC was negatively correlated with tumor size (Rho = -0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27((Kip1)) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27((Kip1)) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27((Kip1)) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27((Kip1)) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.
细胞周期蛋白依赖性激酶抑制剂（CDKI）在良性和恶性泌尿系统疾病中的重要性是当前正在深入研究的课题。本研究的目的是分析p27（Kip1）CDKI在良性和恶性肾细胞中的表达，并评估其与不同临床参数之间的可能关联。对24例正常人类肾脏组织和52例肾细胞癌（RCC）组织样本中的p27（Kip1）表达进行了评估和比较。比较了两组之间的表达强度，并分析了其与癌症临床参数的关联。该标志物在正常样本中的表达显著高于RCC样本（P = 0.0045）。RCC中p27（Kip1）的表达强度与肿瘤大小呈负相关（Rho = -0.438，P = 0.0051），并与病理分期和分级相关（分别为P = 0.0488和<0.0001）。有症状疾病的患者其标志物表达明显低于偶然发现的肿瘤（P = 0.030l）。p27（Kip1）表达缺失、病理分期、分级和肿瘤大小是疾病复发的危险因素（分别为P = 0.0072、0.0011、0.0467和<0.0001）以及患者生存的危险因素（分别为P = 0.0021、0.0106、0.0151和0.0021）。通过Cox多变量分析，p27（Kip1）表达缺失（风险比9.3，P = 0.002）和肿瘤大小（风险比5.9，P = 0.015）是癌症特异性生存情况的预测指标。与正常肾组织相比，RCC中p27（Kip1）的表达显著降低。其表达强度与临床参数相关：肿瘤大小、分期、分级和疾病表现。p27（Kip1）表达缺失是疾病复发的危险因素，也是癌症特异性生存情况的最强预测指标。
