PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma
OBJECTIVES: Immune checkpoint blockade using inhibitors of programmed death-1 have shown promise in early phase clinical trials in NSCLC and programmed death-ligand 1 (PD-L1) tumoral expression could potentially be a useful predictive marker. Data reporting the prevalence of PD-L1 expression in NSCLC and clinicopathologic associations is very limited. We sought to determine the frequency of PD-L1 expression in NSCLC and investigate associations with clinicopathologic features and patient outcome. MATERIALS AND METHODS: PD-L1 expression was analyzed using immunohistochemistry (Merck; clone 22C3) in 678 stages I-III NSCLC and 52 paired nodal metastases using tissue microarrays. Tumors with >/=50% cells showing positive membrane staining were considered to have high expression of PD-L1. RESULTS: PD-L1 expression of any intensity was identified in 32.8% of cases. High PD-L1 expression was found in 7.4% of NSCLC. Squamous cell carcinomas (8.1%) and large cell carcinomas (12.1%) showed high PD-L1 expression more commonly than adenocarcinomas (5.1%) but this was not statistically significant (p=0.072). High PD-L1 expression was associated with younger patient age and high tumor grade (p<0.05). There was no association with gender, tumor size, stage, nodal status, EGFR or KRAS mutation status. In multivariate analysis, patients with high PD-L1 expression had significantly longer overall survival (p<0.05). CONCLUSIONS: PD-L1 is expressed at high levels in a significant proportion of NSCLC and appears to be a favorable prognostic factor in early stage disease. As there are potential sampling limitations using tissue microarrays to assess heterogeneously expressed biomarkers, and as the results may differ in advanced stage disease, further studies are recommended.
|Authors||Cooper, W. A.; Tran, T.; Vilain, R. E.; Madore, J.; Selinger, C. I.; Kohonen-Corish, M.; Yip, P.; Yu, B.; O'Toole, S. A.; McCaughan, B. C.; Yearley, J. H.; Horvath, L. G.; Kao, S.; Boyer, M.; Scolyer, R. A.|
|Publisher Name||LUNG CANCER|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/26024796|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12994|