Author of

• 25901

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  MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy (ID 913)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 10:30 - 12:00, Room 202 BD

  • 26004

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    MA12.11 - Analysis of Angiogenic and Stromal Biomarkers in a Large Malignant Mesothelioma Cohort (ID 12234)

    11:40 - 11:45  |  Author(s): Marzena Walkiewicz
    • Abstract
    • Presentation
    • Slides

    Background
    

    Malignant mesothelioma (MM) is an aggressive malignancy of the pleura and other mesothelium membranes. Agents targeting vascular endothelial growth factor (VEGF) receptor such as bevacizumab; and multi-kinase inhibitors like 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 therapies, it is important to evaluate angiogenic and stromal markers in MM to assess their associated prognostic implications.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    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. 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. The discriminatory threshold was set for each IHC stain (usually the median score) and samples were classified as low (below median) or high expression (above median). 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.

    4c3880bb027f159e801041b1021e88e8 Result
    

    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-CC high (≥150) was seen in 203/310 (65%) of all samples but was higher in epithelioid subtype [129/203 (64%)]. 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 and 73/127 (57.5%) are of epithelioid histology.

    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.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    High PDGF-CC expression and CD31 scores are associated with poor survival in MM. Abrogating these pathways may have prognostic implications.

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