High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma

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dc.contributor.author Ollila, Hely
dc.contributor.author Paajanen, Juuso
dc.contributor.author Wolff, Henrik
dc.contributor.author Ilonen, Ilkka
dc.contributor.author Sutinen, Eva
dc.contributor.author Välimäki, Katja
dc.contributor.author Östman, Arne
dc.contributor.author Anttila, Sisko
dc.contributor.author Kettunen, Eeva
dc.contributor.author Räsänen, Jari
dc.contributor.author Kallioniemi, Olli
dc.contributor.author Myllärniemi, Marjukka
dc.contributor.author Mäyränpää, Mikko I.
dc.contributor.author Pellinen, Teijo
dc.date.accessioned 2022-02-16T12:33:01Z
dc.date.available 2022-02-16T12:33:01Z
dc.date.issued 2021-09
dc.identifier.citation Ollila , H , Paajanen , J , Wolff , H , Ilonen , I , Sutinen , E , Välimäki , K , Östman , A , Anttila , S , Kettunen , E , Räsänen , J , Kallioniemi , O , Myllärniemi , M , Mäyränpää , M I & Pellinen , T 2021 , ' High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma ' , The Journal of pathology. Clinical research , vol. 7 , no. 5 , pp. 482-494 . https://doi.org/10.1002/cjp2.218
dc.identifier.other PURE: 164801444
dc.identifier.other PURE UUID: 937cafd8-d8b1-4a55-86f9-29fd5ab5e31a
dc.identifier.other WOS: 000647414900001
dc.identifier.other ORCID: /0000-0001-9343-0867/work/108462865
dc.identifier.other ORCID: /0000-0002-0877-9640/work/108466621
dc.identifier.other ORCID: /0000-0002-8149-3550/work/108466814
dc.identifier.uri http://hdl.handle.net/10138/340423
dc.description.abstract Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location-specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all-cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet-derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p <0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00-1.03 and HR = 1.05, 95% CI = 1.00-1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence-based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof The Journal of pathology. Clinical research
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject mesothelioma
dc.subject prognosis
dc.subject platelet-derived growth factor receptor beta
dc.subject fibroblast
dc.subject CLASSIFICATION
dc.subject PHASE-II
dc.subject FIBROBLASTS
dc.subject BREAST-CANCER
dc.subject TRIAL
dc.subject GRADING SYSTEM
dc.subject POOR-PROGNOSIS
dc.subject PROGNOSTIC-SIGNIFICANCE
dc.subject IMATINIB MESYLATE
dc.subject IMMUNOHISTOCHEMISTRY
dc.subject 3111 Biomedicine
dc.subject 3122 Cancers
dc.title High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization University of Helsinki
dc.contributor.organization HUS Heart and Lung Center
dc.contributor.organization Keuhkosairauksien yksikkö
dc.contributor.organization Helsinki University Hospital Area
dc.contributor.organization INDIVIDRUG - Individualized Drug Therapy
dc.contributor.organization Faculty of Medicine
dc.contributor.organization Medicum
dc.contributor.organization Department of Pathology
dc.contributor.organization Department of Surgery
dc.contributor.organization Clinicum
dc.contributor.organization III kirurgian klinikka
dc.contributor.organization Department of Medicine
dc.contributor.organization Research Programs Unit
dc.contributor.organization Precision Systems Medicine
dc.contributor.organization HUSLAB
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1002/cjp2.218
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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