Angiotensin II type I receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival

Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type I angiotensin II receptors (AT₁R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT₁R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT₁R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT₁R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type I angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type I angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT₁R, the overall survival and progression-free survival were significantly poor (P = 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT₁R, although VEGF, but not AT₁R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT₁R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.