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

M Frödin, A Mezheyeuski, S Corvigno… - British journal of …, 2017 - nature.com
M Frödin, A Mezheyeuski, S Corvigno, U Harmenberg, P Sandström, L Egevad…
British journal of cancer, 2017nature.com
Background: Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-
angiogenic treatment with multi-tyrosine-kinase-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 PDGFR-β, as a determinant of prognosis in other tumour
types. Methods: This work explored the impact on prognosis of vascular characteristics in …
Abstract
Background:
Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-angiogenic treatment with multi-tyrosine-kinase-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 PDGFR-β, 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 α-SMA or PDGFR-β.
Results:
Perivascular expression of PDGFR-β and α-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-β and α-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-β 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-β. 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.
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