16613 PD-1, PD-L1, and BIM as predictors of sentinel lymph node metastasis in primary cutaneous melanoma

Abstract

Here we tested whether the expression of the immune checkpoint program cell death protein 1 (PD-1), its ligand PD-L1, or its downstream effector Bcl-2 interacting mediator of cell death (BIM) in primary cutaneous melanoma (PCM) diagnostic biopsy tissue is associated with PCM metastasis to sentinel lymph nodes (SLN). We obtained a cohort of 754 patients with thin and intermediate thickness PCM who underwent SLN biopsy within 90 days of diagnosis. We then used real-time quantitative PCR to quantify gene expression in diagnostic biopsy tissue. We found that the expression of BIM but not PD-1 or PD-L1 was significantly associated with SLN metastasis (P = .004). The absence of a significant association between PD-1 and PD-L1 expression in PCM diagnostic biopsy tissue and SLN metastasis was confirmed by immunohistochemistry in a cohort subset. Predictive models that considered the clinicopathologic variables Breslow depth and age were not significantly improved by adding the gene expression variables BIM, PD-1, or PD-L1. In contrast, a highly significant improvement in the predictive ability among the 754 studied patients was observed with the CP-GEP model from SkylineDx. We conclude that while the PD-1/PD-L1 immune checkpoint drives immune tolerance and disease progression its global expression in PCM diagnostic biopsy tissue is not associated with regional metastasis.