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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363931/
https://www.ncbi.nlm.nih.gov/pubmed/33955203
http://dx.doi.org/10.1002/cjp2.218
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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
author_facet 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
author_sort Ollila, Hely
collection PubMed
description 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.
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spelling pubmed-83639312021-08-23 High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma 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 J Pathol Clin Res Original Articles 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. John Wiley & Sons, Inc. 2021-05-06 /pmc/articles/PMC8363931/ /pubmed/33955203 http://dx.doi.org/10.1002/cjp2.218 Text en © 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
title High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
title_full High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
title_fullStr High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
title_full_unstemmed High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
title_short High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
title_sort high tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363931/
https://www.ncbi.nlm.nih.gov/pubmed/33955203
http://dx.doi.org/10.1002/cjp2.218
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