Abstract 1557: Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort
Authors: Chia Puey Ling , Russell Prudence , Murone Carmel , Walkiewicz Marzena , Eriksson Ulf , Scott Andrew , John Thomas 
Published: August 2018

Abstract
Background:
Malignant mesothelioma (MM) is an aggressive malignancy of the pleura and other serosal membranes originating from mesothelial cells. Agents targeting vascular endothelial growth factor (VEGF) receptor 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. In the setting of these new therapeutic agents, it is important to evaluate VEGF, PDGF and CD31 (angiogenesis marker) in MM to assess their associated prognostic implications.
Methods:
Tissue microarrays (TMAs) were created from formalin-fixed, paraffin-embedded tissue samples obtained from 326 patients who underwent surgical resection or biopsy for MM between 1988 and 2014. The expression of PDGF-C, VEGF and CD31 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 viewed at various magnifications by a pathologist and an investigator. The discriminatory threshold was set for each IHC stain (usually the median score) and the samples were classified as low (below median score) or high expression (above median score) for each of stain. CD31 was evaluated via Chalkley's method (objective method of measuring vascularity) to evaluate microvessel density. We evaluated the association between expression of the biomarkers, clinicopathological factors and outcomes, in patients with MM.
Results:
The histological subtypes comprised of 203/325 (62.5%) epithelioid; 72/325 (22.2%) biphasic; 42/325 (12.9%) sarcomatoid, or indeterminate. The median age was 67 (range 24-88) with Male: Female ratio of 266: 53. CD31 high (≥5) was seen in only 31/302 (10.3%) irrespective of histology (13/31 (42%) epithelioid; 10/31 (32%) sarcomatoid; 7/31 (23%) biphasic; 1/31 indeterminate). PDGF-C high IHC (≥150) was seen in 203 /310 (65%) of all samples but was higher in epithelioid histology (129/203 (64%) epithelioid; 45/203 (22%) biphasic and 28/203 (13.8%) sarcomatoid; 1/203 indeterminate). VEGF high (≥200) was seen in 219/322 (68%) of all MM and was also higher in epithelioid histology [143/209 (68%)]. There was no association of VEGF IHC with survival nor differences between histological subtypes. There was a non-significant trend towards poorer survival in epithelioid tumours with increased PDGFC expression (HR 0.7928; 95% CI 0.5958 to 1.055, P=0.0434). 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-C and 20/31 (64%) with high VEGF scores.
Conclusions:
High PDGF-C expression and CD31 scores are associated with poor survival in MM. Abrogating these pathways may have prognostic implications.
Citation Format: Puey Ling Chia, Prudence Russell, Carmel Murone, Marzena Walkiewicz, Ulf Eriksson, Andrew Scott, Thomas John. Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1557.