title: Loss of p27(Kip1) CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer.
abstract: 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.
authors.affiliation: Departments of Adult Urology, National Centre of Urology, Tsinandali st 9, 0144, Tbilisi, Georgia.
authors.forename: Ambrosi
authors.initials: A
authors.lastname: Pertia
authors.forename: David
authors.initials: D
authors.lastname: Nikoleishvili
authors.forename: Omar
authors.initials: O
authors.lastname: Trsintsadze
authors.forename: Nino
authors.initials: N
authors.lastname: Gogokhia
authors.forename: Laurent
authors.initials: L
authors.lastname: Managadze
authors.forename: Archil
authors.initials: A
authors.lastname: Chkhotua
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27