Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma
(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.
(Less)
- author
- Frödin, Magnus ; Mezheyeuski, Artur ; Corvigno, Sara ; Harmenberg, Ulrika ; Sandström, Per-Erik ; Egevad, Lars ; Johansson, Martin LU and Östman, Arne
- organization
- publishing date
- 2017-01-17
- 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
-
- pmid:27931046
- wos:000394443700007
- scopus:85001760505
- 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
- 2024-03-31 05:21:20
@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}},
keywords = {{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}},
doi = {{10.1038/bjc.2016.407}},
volume = {{116}},
year = {{2017}},
}