PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome.

Sandra Lassalle,Boris Scheller,Stéphanie Baillif,Sacha Nahon-Esteve,Paul Hofman,Eric Frouin,Camille Boulagnon-Rombi,Nicolas Josselin,Nathalie Cassoux,Raymond Barnhill

doi:10.3390/ijms21239147

Abstract

Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.

Highlights

Ocular melanomas include uveal melanoma and conjunctival melanoma (CM)
We evaluated the expression of Programmed death-ligand-1 (PD-L1), CD8, programmed death-1 (PD-1) in Conjunctival melanoma (CM) and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria
We found a significant correlation between the positivity to PD-L1 (SP142 and SP263 clones) and CD8+ Tumour-Infiltrating Lymphocyte (TIL) and between the positivity of PD-L1 (SP142 and SP263 clones) and PD-1+ TILs

Summary

Introduction

Ocular melanomas include uveal melanoma and conjunctival melanoma (CM). CM is much more similar to cutaneous melanoma than to uveal melanoma at the molecular level, and considering the clinical evolution. As for cutaneous melanoma, CM can be metastatic to all organs, while the most common metastatic site of uveal melanoma is the liver. Uveal and CM display distinct genetic features, which should be taken into consideration when making clinical decisions. Genetic studies have reported mutations in BRAF, NRAS, and KIT, and implication of ultraviolet radiation as a risk factor for CM [4,5,6,7,8,9,10]. No BRAF or NRAS mutations or UV-induced mutational signatures have been described in uveal melanoma [12]

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