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A. Salcedo
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-004 - Genome-Wide Copy Number Aberrations in Mesothelioma and Its Correlation with Tumour Microenvironment including PD-L1 Expression (ID 4506)
14:30 - 14:30 | Author(s): A. Salcedo
- Abstract
Background:
Recent clinical studies have demonstrated positive correlation between tumour mutational burden and response to immune checkpoint inhibitors (CPI) in several malignancies. Although initial reports of some CPI in Malignant Mesothelioma (MM) have shown promise, the rate of somatic mutations in MM is known to be low and copy number aberrations (CNA) are the prominent genetic alterations. Using a large cohort of MM patients, we investigated CNA, PD-L1 expression and the surrounding immune infiltrates and correlated these parameters to clinicopathological features.
Methods:
Tissue microarrays (TMA) were constructed and stained with PD-L1 (E1L3N,CST, Massachusetts), CD4, CD8 and Foxp3 antibodies. PD-L1 positivity (PD-L1+) was defined as >5% membranous staining regardless of intensity and high positive as >50%. Genomic DNA was obtained from tumour cores of a representative subset (100 patients) and used for genome-wide copy number analysis. Percent genome aberrated (PGA) was computed for each sample as the total number of base pairs within altered regions, divided by the total number of base pairs in each region included in the array. Correlations of PGA, CNA profile and individual aberration (loss/gain) frequency with parameters including PD-L1 expression and survival were explored.
Results:
Amongst 329 patients evaluated, the median age was 67 years and most were male 274(83.2%). Epithelioid histology (N=203; 62.9%) was the commonest. PD-L1 positivity was seen in 41.7% with high positivity in 9.6%. PD-L1+ correlated with non–epitheloid histology (P=<0.0001) and increased infiltration with CD4, CD8 and FOXP3 lymphocytes. High PD-L1 expression correlated with worse prognosis (HR=2.37; 95%CI: 1.57-3.56; P=<0.0001) on univariate analysis but the effect was found to be time dependent. Neither PGA (P=0.57) nor CNA profile (P=0.76) were found to be associated with PD-L1 expression. After correction for multiple testing, no individual CNA count was significantly associated with PD-L1 status. Although epithelioid histology had higher PGA (P=0.04), high PGA was associated with poorer survival (HR=2.01; 95% CI: 1.24-3.26; P=0.004). This was also true when only epithelioid tumours (n=63) were considered.
Conclusion:
Increased genomic alterations in MM did not correlate with PD-L1 expression but was associated with poorer survival. High PD-L1 expression was associated with non-epithelioid MM, poor clinical outcome and increased immunological infiltrates.
