Expression of the cell cycle proteins p21, p27, and pRb in clear cell renal cell carcinoma and their prognostic significance

Abstract

Objectives. To determine whether p21, p27, and pRb can predict disease progression in clear cell renal cell carcinoma. Methods. The expression of three negative regulators of the cell cycle, the retinoblastoma gene product (pRb), the WAF1/Cip1 gene product (p21), and the Kip1 gene product (p27), was investigated by immunohistochemistry on paraffin sections from 104 formalin-fixed clear cell carcinoma specimens and related to p53 overexpression, the clinicopathologic parameters, and survival. Results. pRb expression was not associated with tumor stage, but the correlation with p27 and p21 positivity was statistically significant ( r = 0.26, P = 0.008 and r = 0.3, P = 0.002, respectively). Tumors representing p53 overexpression showed a higher pRb labeling index compared with p53-negative tumors ( P = 0.0004). p21 protein expression correlated significantly with p27 positivity ( r = 0.2, P = 0.04) and was associated with p53 overexpression ( P = 0.0005), but did not correlate with tumor stage or grade. No association could be found between p27 positivity and tumor grade, tumor stage, or p53 overexpression. In univariate survival analysis, an increased pRb positivity ( P = 0.002) and a low p27 expression ( P = 0.0001) predicted a poor outcome, especially if combined with p53 overexpression ( P = 0.004 and P = 0.0002, respectively). p21 did not give any prognostic information. Moreover, in multivariate analysis, pRb and p27 were revealed to be statistically significant. Conclusions. The results of our study indicate that in clear cell renal cell carcinoma, the cell cycle proteins p27 and pRb are powerful and independent prognostic factors and that p21 has no predictive value.