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Title: Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort.
Austin Authors: Chia, Puey Ling ;Russell, Prudence;Asadi, Khashi;Thapa, Bibhusal ;Gebski, Val;Murone, Carmel ;Walkiewicz, Marzena;Eriksson, Ulf;Scott, Andrew M ;John, Thomas 
Affiliation: Department of Pathology, St Vincent's Hospital, Melbourne, Australia
Faculty of Medicine, University of Melbourne, Melbourne, Australia
Australia National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia
Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Melbourne, Australia
Molecular Imaging and Therapy
Faculty of Medicine, University of Melbourne, Melbourne, Australia
Medical Oncology
Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Issue Date: Dec-2020
Date: 2020-10-01
Publication information: Lung Cancer 2020; 150: 1-8
Abstract: Malignant 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.
DOI: 10.1016/j.lungcan.2020.09.022
Journal: Lung Cancer
PubMed URL: 33035778
Type: Journal Article
Subjects: fibroblast growth factor receptor
malignant mesothelioma
microvessel density
platelet-derived growth factor
vascular endothelial growth factor
Appears in Collections:Journal articles

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