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PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics.
MedLine Citation:
PMID:  25223485     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Programmed cell death ligand 1 (PD-L1) is a cell surface molecule that plays a critical role in suppressing immune responses, mainly through binding of the PD-1 receptor on T lymphocytes. PD-L1 may be expressed by metastatic melanoma. However, its clinical and biological significance remains unclear. Here, we investigated whether expression of PD-L1 in metastatic melanoma identifies a biologically more aggressive form of the disease, carrying prognostic relevance.
PATIENTS AND METHODS: PD-L1 expression was analyzed by immunohistochemistry using two different antibodies in primary tumors and paired metastases from 81 melanoma patients treated at a single institution. Protein expression levels were correlated with PD-L1 mRNA, BRAF mutational status and clinical outcome. PD-L1(+) and PD-L1(-) subsets of the A375 cell line were stabilized in vitro and compared using gene expression profiling and functional assays. Results were confirmed using xenograft models.
RESULTS: PD-L1 membrane positivity was detected in 30/81 (37%) of patients. By multivariate analysis, Breslow thickness and PD-L1 membrane positivity were independent risk factors for melanoma-specific death [PD-L1 5% cutoff (HR 3.92, CI 95% 1.61-9.55 p< 0.003), PD-L1 as continuous variable (HR 1.03, CI 95% 1.02-1.04 p< 0.002)]. PD-L1 expression defined a subset of the BRAF-mutated A375 cell line characterized by a highly invasive phenotype and by enhanced ability to grow in xenograft models.
CONCLUSIONS: PD-L1 is an independent prognostic marker in melanoma. If confirmed, our clinical and experimental data suggest that PD-L1(+) melanomas should be considered a disease subset with distinct genetic and morpho-phenotypic features, leading to enhanced aggressiveness and invasiveness.
Authors:
D Massi; D Brusa; B Merelli; M Ciano; V Audrito; S Serra; R Buonincontri; G Baroni; R Nassini; D Minocci; L Cattaneo; E Tamborini; A Carobbio; E Rulli; S Deaglio; M Mandalà
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-15
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  -     ISSN:  1569-8041     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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