Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: A systematic analysis of primary and metastatic tumor tissue

Objectives. To investigate the histologic subtypes of renal cell carcinoma (RCC) with respect to differences in immunoreactivity for p53 and its impact on prognosis. The prognostic significance of p53 in RCC remains to be defined. Methods. A total of 188 primary RCC and 58 RCC metastasis specimens were stained immunohistochemically for p53 overexpression using a tissue microarray technique. p53 overexpression was analyzed semiquantitatively with respect to its association with pT stage, grade, histologic subtype, and sex using the chi-square test or Fisher's exact test. The impact on metastasis-free survival was analyzed using the Kaplan-Meier method and log-rank test. For conventional RCC, a multivariate analysis, including pT stage, grade, and p53 immunoreactivity was performed. Results. Sufficient tumor tissue was present in 184 (97.9%) of 188 primary and 56 (96.6%) of 58 metastatic cases. p53 overexpression was found in 42 (22.8%) of 184 primary RCC specimens and in 29 (51.8%) of 56 metastasis specimens (P = 0.0001). p53 overexpression for papillary, chromophobe, and conventional RCC was 70.0%, 27.3%, and 11.9%, respectively (P < 0.0001). No association of p53 immunoreactivity with the other parameters investigated was found. Regarding prognosis, a statistically significant difference in metastasis-free survival between p53-positive and p53-negative tumors was found only for conventional RCC (P = 0.0005) and not for the other subtypes (P = 0.19). Multivariate analysis proved grade (P < 0.0001), pT stage (P = 0.01), and p53 overexpression (P = 0.01) to be independent prognostic factors for conventional RCC. Conclusions. p53 overexpression was significantly more frequent in nonconventional RCC subtypes, especially papillary RCC, compared with conventional RCC in our study. However, p53 immunoreactivity is a prognostic marker only for conventional RCC. (C) 2004 Elsevier Inc.