title: Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma.
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.
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Frödin
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Artur
authors.initials: A
authors.lastname: Mezheyeuski
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Corvigno
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Harmenberg
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Sandström
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.affiliation: Department of Translational Medicine, Clinical Pathology, Lund University, Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Pathology-Oncology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Östman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000378:metabolism; D011379:Prognosis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D020797:Receptor, Platelet-Derived Growth Factor beta