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

Frödin, Magnus; Mezheyeuski, Artur; Corvigno, Sara; Harmenberg, Ulrika; Sandström, Per-Erik; Egevad, Lars; Johansson, Martin LU and Östman, Arne (2017) In British Journal of Cancer 116(2). p.195-201
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... (More)

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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type
Contribution to journal
publication status
published
subject
keywords
molecular biomarkers, pericyte heterogeneity, renal cancer, targeted therapy, vascular biology
in
British Journal of Cancer
volume
116
issue
2
pages
7 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85001760505
  • wos:000394443700007
ISSN
0007-0920
DOI
10.1038/bjc.2016.407
language
English
LU publication?
yes
id
be01924e-db54-4a9b-9602-f6dc9564519d
date added to LUP
2017-03-03 08:08:08
date last changed
2018-01-07 11:53:51
@article{be01924e-db54-4a9b-9602-f6dc9564519d,
  abstract     = {<p>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.</p>},
  author       = {Frödin, Magnus and Mezheyeuski, Artur and Corvigno, Sara and Harmenberg, Ulrika and Sandström, Per-Erik and Egevad, Lars and Johansson, Martin and Östman, Arne},
  issn         = {0007-0920},
  keyword      = {molecular biomarkers,pericyte heterogeneity,renal cancer,targeted therapy,vascular biology},
  language     = {eng},
  month        = {01},
  number       = {2},
  pages        = {195--201},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma},
  url          = {http://dx.doi.org/10.1038/bjc.2016.407},
  volume       = {116},
  year         = {2017},
}