Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort

Puey Ling Chia; Prudence Russell; Khashi Asadi; Bibhusal Thapa; Val Gebski; Carmel Murone; Marzena Walkiewicz; Ulf Eriksson; Andrew M Scott; Thomas John

doi:10.1016/j.lungcan.2020.09.022

Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort

Lung Cancer. 2020 Dec:150:1-8. doi: 10.1016/j.lungcan.2020.09.022. Epub 2020 Oct 1.

Authors

Affiliations

¹ Department of Medical Oncology, Austin Health, Melbourne, Australia; Olivia-Newton John Cancer Research Institute, Melbourne, Australia; Faculty of Medicine, University of Melbourne, Melbourne, Australia. Electronic address: Puey_Ling_CHIA@ttsh.com.sg.
² Department of Pathology, St Vincent's Hospital, Melbourne, Australia.
³ Department of Pathology, Austin Hospital, Melbourne, Australia.
⁴ Olivia-Newton John Cancer Research Institute, Melbourne, Australia; Faculty of Medicine, University of Melbourne, Melbourne, Australia.
⁵ Australia National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
⁶ Olivia-Newton John Cancer Research Institute, Melbourne, Australia.
⁷ Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
⁸ Olivia-Newton John Cancer Research Institute, Melbourne, Australia; Faculty of Medicine, University of Melbourne, Melbourne, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Australia; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia.
⁹ Department of Medical Oncology, Austin Health, Melbourne, Australia; Olivia-Newton John Cancer Research Institute, Melbourne, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Australia.

PMID: 33035778
DOI: 10.1016/j.lungcan.2020.09.022

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: fibroblast growth factor receptor; malignant mesothelioma; microvessel density; platelet-derived growth factor; vascular endothelial growth factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Humans
Lung Neoplasms*
Mesothelioma, Malignant*
Prognosis
Vascular Endothelial Growth Factor A

Substances

Biomarkers
Vascular Endothelial Growth Factor A