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

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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

Title: High tumor cell platelet-derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
Author: Ollila, Hely; Paajanen, Juuso; Wolff, Henrik; Ilonen, Ilkka; Sutinen, Eva; Välimäki, Katja; Östman, Arne; Anttila, Sisko; Kettunen, Eeva; Räsänen, Jari; Kallioniemi, Olli; Myllärniemi, Marjukka; Mäyränpää, Mikko I.; Pellinen, Teijo
Contributor organization: Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
University of Helsinki
HUS Heart and Lung Center
Keuhkosairauksien yksikkö
Helsinki University Hospital Area
INDIVIDRUG - Individualized Drug Therapy
Faculty of Medicine
Medicum
Department of Pathology
Department of Surgery
Clinicum
III kirurgian klinikka
Department of Medicine
Research Programs Unit
Precision Systems Medicine
HUSLAB
Date: 2021-09
Language: eng
Number of pages: 13
Belongs to series: The Journal of pathology. Clinical research
DOI: https://doi.org/10.1002/cjp2.218
URI: http://hdl.handle.net/10138/340423
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.
Subject: mesothelioma
prognosis
platelet-derived growth factor receptor beta
fibroblast
CLASSIFICATION
PHASE-II
FIBROBLASTS
BREAST-CANCER
TRIAL
GRADING SYSTEM
POOR-PROGNOSIS
PROGNOSTIC-SIGNIFICANCE
IMATINIB MESYLATE
IMMUNOHISTOCHEMISTRY
3111 Biomedicine
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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