Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and growth

Background and Objectives: PTEN is a candidate tumor suppressor gene in a variety of malignant tumors, including renal cell carcinoma (RCC). PTEN regulates cell cycle progression and cell survival in vivo. However, the role of PTEN alterations and their association with tumor growth and behavior in patients with RCC has not been well established. The aim of our study was to evaluate PTEN expression in RCC and its correlation with clinicopathologic features, cell proliferation, and apoptosis. Methods: Sixty-seven RCC specimens were examined immunohistochemically with anti-PTEN antibody. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67 antibody. Results: Twenty-one (31.3%) of the 67 RCCs showed reduced PTEN expression. The apoptotic index (AI) varied from 0.2 to 25.5%, and the Ki-67 index (KI) ranged from 1.6 to 69.8%. Reduced PTEN expression correlated with TNM stage (P < 0.05) and nuclear grade (P < 0.05). Tumors with reduced PTEN expression had a significantly higher KI than those with normal PTEN expression (P < 0.01). By univariate analysis, nuclear grade (P = 0.0005), TNM stage (P < 0.0001), AI (P = 0.0220), KI (P = 0.0002), and reduced PTEN expression (P < 0.0001) were associated with shortened survival. However, TNM stage was the only independent prognostic factors by multivariate analysis (P = 0.0007). Conclusions: Our results suggest that PTEN expression is frequently reduced in advanced RCC. The PTEN gene seems to be important for the growth suppression of RCC, by inhibiting cell proliferation. (C) 2003 Wiley-Liss, Inc.