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

Biomarkers Humans Lung Neoplasms Mesothelioma, Malignant Prognosis Vascular Endothelial Growth Factor A
fibroblast growth factor receptor malignant mesothelioma microvessel density platelet-derived growth factor vascular endothelial growth factor

Journal

Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805

Informations de publication

Date de publication:
12 2020
Historique:
received: 08 07 2020
revised: 04 09 2020
accepted: 25 09 2020
pubmed: 10 10 2020
medline: 22 6 2021
entrez: 9 10 2020
Statut: ppublish

Résumé

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.

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.lungcan.2020.09.022 PMID: 33035778
pubmed: 33035778
pii: S0169-5002(20)30632-2
doi: 10.1016/j.lungcan.2020.09.022
pii:
doi:

Substances chimiques

Biomarkers 0
Vascular Endothelial Growth Factor A 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1-8

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Puey Ling Chia (PL)

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.

Prudence Russell (P)

Department of Pathology, St Vincent's Hospital, Melbourne, Australia.

Khashi Asadi (K)

Department of Pathology, Austin Hospital, Melbourne, Australia.

Bibhusal Thapa (B)

Olivia-Newton John Cancer Research Institute, Melbourne, Australia; Faculty of Medicine, University of Melbourne, Melbourne, Australia.

Val Gebski (V)

Australia National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.

Carmel Murone (C)

Olivia-Newton John Cancer Research Institute, Melbourne, Australia.

Marzena Walkiewicz (M)

Olivia-Newton John Cancer Research Institute, Melbourne, Australia.

Ulf Eriksson (U)

Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.

Andrew M Scott (AM)

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.

Thomas John (T)

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.

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