Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma

Abstract

Background: The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors. Methods: Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT-PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS). Results : A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P< 0.001, AT2-R: P< 0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P< 0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P< 0.006) and cancer stage (P< 0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P< 0.01 and P< 0.001 respectively). By qRT-PCR, AT1-R but not AT2-R mRNA were downregulated (P< 0.001 and P0.118, respectively). Conclusion : Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy. © 2010 Cancer Research UK.