Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma

Background: Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-angiogenic treatment with multi-tyrosinekinase-inhibitor, is used for first-line treatment of metastatic disease. Variations in vascular characteristics are likely to contribute to variations in intrinsic aggressiveness of the disease. Emerging studies are identifying perivascular status, including perivascular PD, as a determinant of prognosis in other tumour types. Methods: This work explored the impact on prognosis of vascular characteristics in RCC through analyses of a population-based collection of tumours from surgery-alone-treated patients. The quantitative data from a panel of vascular metrics were obtained through computerised image analysis of sections double-stained for expression of the endothelial cell marker CD34 together with perivascular markers alpha-SMA or PDGFR-beta. Results: Perivascular expression of PDGFR-beta and alpha-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-beta and alpha-SMA as well as low vessel density was significantly associated with short survival in uni-and multivariate analyses. Subgroup analyses demonstrated that the prognostic impact of the perivascular markers was particularly prominent in the T4-subgroup. A novel metric, related to PDGFR-beta perivascular heterogeneity, was also associated with prognosis in uni- and multi-variate analyses. This novel metric also acted as a prognosis marker in ovarian cancer. Conclusions: The study demonstrates previously unrecognised associations between RCC survival and the absolute levels, and variability, of perivascular PDGFR-beta. This marker should be further explored in other RCC cohorts. Findings also suggest mechanistic analyses and studies on the relationship between perivascular status and efficacy of multi-tyrosine-kinase-inhibitors.