Detection of p53 protein as a prognostic indicator in clear cell renal cell carcinoma

Renal cell carcinoma (RCC) has been characterized based on histology, stage and grading to predict behavior and guide therapy ; however RCC is still unpredictable and regardless of tumor size and histology, the molecular attributes of a RCC can determine its risk of recurrence and metastasis (1). Several molecular markers have been investigated for their role in the pathogenesis and progression of RCC. Among them, p53 gene have been reported with wide variation in the literature, and its prognostic significance for this tumor is still unknown (2). Mutations of p53 permit damaged cells to persist in the cell-cycle, thereby promoting carcinogenesis. Mutant p53 protein has a long half-life, and therefore can be detected by immunohistochemistry as a nuclear stain (3, 4, 5). The aim of this retrospective immunohistochemical study was to examine the associations between p53 immunostaining and tumor grade, size and stage (pT), proliferation rate and survival of patients with clear cell renal cell carcinoma (CCRCC). Tissue microarrays (TMA) were built from the cohort of 94 archival formalin fixed paraffin embedded CCRCC. Immunohistochemistry was performed for p53 and Ki67 using the D07 monoclonal antibody and MIB 1. The staining was evaluated as a percentage of nuclear positive tumor cells per 500 cells in each TMA. The median percentage of p53 positive tumor cells was 40.5 (12-90.9). High expression of p53 protein was associated with lower pT stage and tumor size smaller then 7 cm, while there was no correlation with Ki 67 proliferation rate and nuclear grade. Log-rank test did not connect the survival and p53 median split on higher and lower percentage of positive cells in CCRCC (Table 1). Studies show that over-expression of p53 in RCC is frequent and occurs in about 36% of 97cases (6), and in larger series, about 29.5% of 246 tumors , irrespective of the type of RCC.). In the study of Zigeuner et al, p53 multivariate analysis showed a correlation with tumor grade and stage of disease and the period of survival without metastases only in the group of CCRCC, so p53 proved to be an independent prognostic factor that predicts worse disease outcome. The same results was achieved by Ulman and coworkers who concluded that mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.(2). Study of Iranian author Kabir and colleagues in a group of 125 RCC with different histology found no connection between p53 over-expression with relevant clinicopathological prognostic factors (9). It is likely that the mechanism of over-expression of p53 and its activity in various types of RCC, especially in CCRCC is different than in other types of cancer what was shown by Gurova et al. who hypothesize that RCC cells may use an existing kidney-specific mechanism of p53 attenuation to achieve complete inhibition of the p53 pathway (10). Further studies are needed to determinethe impact of p53 expression and clinical outcomes in RCC.