Immunoreactivity of p27(Kip1), cyclin D3, and Ki67 in conventional renal cell carcinoma

Abstract

The goal of the study was to evaluate expression of the cell-cycle regulatory proteins (p27(Kip1) and cyclin D3) and proliferation marker Ki67 in normal human kidneys and renal cell carcinoma (RCC) tissues. Intensity of the markers' expression was prospectively studied and compared between normal and RCC tissue samples. Association was analyzed with cancer clinical parameters. p27(Kip1) was significantly upregulated in normal compared with in RCC samples. Immunoreactivity of the protein negatively correlated with tumor size and was associated with pathological stage and grade. Patients with symptomatic disease had significantly less marker expression than those with incidentally discovered tumors. Intensity of Ki67 staining positively correlated with primary tumor size and associated with disease stage and grade. Cyclin D3 immunoreactivity positively correlated with tumor size. Loss of p27(Kip1) expression, pathological stage, grade, and tumor size were risk factors for disease recurrence (P = 0.0072, 0.0011, and 0.0467, and P < 0.0001, respectively) and patient death (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. In conclusion, intensity of the markers' expression in RCC is associated with tumour clinical parameters (size, stage, grade, and disease presentation type). Loss of p27(Kip1) expression is a risk factor for the disease recurrence and cancer-related patient death.