Claudins as Prognostic Factors for Renal Cell Cancer

Background: Claudins are tight junction proteins and their expression is often different in normal and corresponding tumor cells. In the present study, we determined how the expression of claudins 1-5 and 7 correlated to survival, grade and stage of patients with renal cell cancer (RCC). Patients and Methods: Primary tumor samples were collected retrospectively from 229 RCC patients. Claudins were detected by immunohistochemistry using commercial monoclonal antibodies against claudins 1- 5 and 7. Median survival time was 6.5 years confidence interval (CI) (4.5-8.5, n=224). Kaplan-Meier survival estimated method was used in survival analyses. Results: Positive expression was detected in 62%, 67%, 45%, 55%, 7% and 35% of cases for claudins 1, 2, 3, 4, 5 and 7, respectively. High expression of claudin 2 was observed in 20% of cases while high expression of other claudins was less frequent. Claudins were compared to classical prognostic factors. On cross-tabulation, claudin 1 (p<0.001) and claudin 2 (p=0.009) were significantly associated with lower-grade and higher-grade tumors, respectively. None of the claudins was significantly associated with tumor stage or patient survival. Conclusion: Claudins 1 and 2 were associated with tumor grade. However, none of the claudins was a more powerful prognostic factor than tumor stage. Clinical stage and histological grade are the most powerful prognostic factors in renal cell carcinoma (RCC), although new prognostic markers, including proliferation index (MIB- 1), anti-apoptosis regulator (BCL-2), apoptosis regulator (BAX), Vascular endothelial growth factor (VEGF), and claudins have been promoted (1-4). Although MIB-1 is a proliferation marker generally associated with tumor size, nuclear grade and necrosis, it has not been found to be an independent prognostic factor of RCC (2, 3). The BCL-2 gene has an inhibitory effect on apoptosis while BAX promotes it. Some studies have reported that they have no independent association with the prognosis of patients with RCC (2, 3). In one study, VEGF was an independent prognostic predictor of outcome (4), but the result was not corroborated by a subsequent study, which, however, suggested that VEGF was significantly correlated with tumor stage and grade (5). Tight intercellular junctions lie adjacent to the apical end