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dc.contributor.authorChia, Puey Ling-
dc.contributor.authorRussell, Prudence-
dc.contributor.authorAsadi, Khashi-
dc.contributor.authorThapa, Bibhusal-
dc.contributor.authorGebski, Val-
dc.contributor.authorMurone, Carmel-
dc.contributor.authorWalkiewicz, Marzena-
dc.contributor.authorEriksson, Ulf-
dc.contributor.authorScott, Andrew M-
dc.contributor.authorJohn, Thomas-
dc.identifier.citationLung Cancer 2020; 150: 1-8en
dc.description.abstractMalignant mesothelioma (MM) is an aggressive malignancy of the pleura and other mesothelial membranes. Agents targeting vascular endothelial growth factor (VEGF) such as bevacizumab; and multi-kinase inhibitors such as nintedanib [angiokinase inhibitor of VEGF, platelet-derived growth factor (PDGF) receptor and fibroblast growth factor receptor (FGFR)] have recently demonstrated efficacy in MM. Tissue microarrays (TMAs) were created from formalin-fixed, paraffin-embedded tissue samples obtained from 326 patients with MM who were treated surgically. PDGF-CC, FGFR-1, VEGF and CD31 expression were analysed by immunohistochemical (IHC) staining. The H-score method assigned a score of 0-300 to each sample, based on the percentage of cells stained at different intensities. CD31 was evaluated via Chalkley's method to evaluate microvessel density. We evaluated the association between expression of the biomarkers, clinicopathological factors and outcomes, in patients with MM. CD31 high (≥5) was seen in only 31/302 (10.3%) irrespective of histology. PDGF-CC high (≥150) was seen in 203 /310 (65%) of all samples. VEGF high (≥80) was seen in 219/322 (68%) of all MM with 143/209 (68%) of epithelioid histology. FGFR-1 high (≥40) was seen in 127/310 (41%) of all MM. There was no association of VEGF and FGFR-1 IHC with survival nor differences between histological subtypes. There was a non-significant trend towards poorer survival in epithelioid tumours with increased PDGF-CC expression (OS 18.5 vs 13.2 months; HR 0.7928; 95% CI 0.5958 to 1.055, P = 0.1110). High CD31 score was associated with significantly poorer survival (OS 12 vs 8.6 months; HR 0.48; 95% CI 0.2873 to 0.7941, P = 0.0044). Of the 31 patients with high CD31 scores; 23/31 (74%) were also high for PDGF-CC and 20/31 (64%) with high VEGF scores. CD31 was found to be an independent prognostic factor in multivariate analysis (HR 1.540; 95% CI 1.018 to 2.330; p = 0.041). High CD31 was an independent poor prognostic factor and high PDGF-CC expression was associated with poor survival in MM. Abrogating these pathways may have prognostic implications.en
dc.subjectfibroblast growth factor receptoren
dc.subjectmalignant mesotheliomaen
dc.subjectmicrovessel densityen
dc.subjectplatelet-derived growth factoren
dc.subjectvascular endothelial growth factoren
dc.titleAnalysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort.en
dc.typeJournal Articleen
dc.identifier.journaltitleLung Canceren
dc.identifier.affiliationDepartment of Pathology, St Vincent's Hospital, Melbourne, Australiaen
dc.identifier.affiliationFaculty of Medicine, University of Melbourne, Melbourne, Australiaen
dc.identifier.affiliationAustralia National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Australiaen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.affiliationFaculty of Medicine, University of Melbourne, Melbourne, Australiaen
dc.identifier.affiliationMedical Oncologyen
dc.identifier.affiliationDivision of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Swedenen
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