Angiogenic and stromal biomarkers in malignant mesothelioma

Agents that target VEGF receptors (e.g. bevacizumab) and multi-angiokinase inhibitors (e.g. nintedanib) recently demonstrated efficacy in the treatment of malignant mesothelioma in early phase trials [10, 11].

These findings prompted Chia et al. [12] to assess the prognostic implications of VEGF, PDGF, FGF, and the angiogenesis marker, CD31, in malignant mesothelioma. They used formalin-fixed, paraffin-embedded tissue samples from 329 patients to create tissue microarrays. All patients underwent surgical resection or biopsy for malignant mesothelioma between 1988 and 2014. IHC staining via the H-score method was used to analyse VEGF, PDGF, FGFR-1, and CD31 expression. The discriminatory threshold was set for each IHC stain, and samples were classified as low (below median) or high expression (above median). Chalkey’s method [13] was used to evaluate CD31 IHC microvessel density. The final Chalkey score was the mean of three separate counts.

Out of 302 samples, 31 (10.3%) had a high (≥5) CD31 score, regardless of histology. It was associated with significantly poorer survival in all histology groups (OS 12 vs 8.6 months; HR 0.48; P=0.0044). In the epithelioid subgroup, a high CD31 score was also associated with significantly poorer survival (OS 14.7 vs 10.1 months; HR 0.69, P=0.01). Of 310 tumour samples, 303 (98%) were classified as PDGF-CC IHC positive (>5% cells stained). Of all samples, 203 (65%) had high (≥150) PDGF-CC. However, the rate was higher in tumours with an epithelioid histology (129/203, 64%).

Data showed a non-significant trend toward poorer survival for patients with epithelioid tumours with increased PDGF-CC expression (high ≥150; low <150). OS was 18.5 months vs 13.2 (HR 0.7928; P=0.110). There were no associations between survival and VEGF IHC or FGFR-1 IHC, and no differences between histological subtypes. This evaluation showed significant expression of vascular and stromal biomarkers in malignant mesothelioma, with high PDGF-CC expression and CD31 scores associated with poor survival. Inhibiting these pathways may have prognostic implications.