Patterns of expression and prognostic implication of glycoprotein nonmetastatic protein B (GPNMB) expression in sentinel lymph nodes of melanoma patients

Sentinel lymph node biopsy (SLNB) is a critical procedure in the management of melanoma, offering prognostic information and guiding adjuvant therapy. Glycoprotein nonmetastatic melanoma protein B (GPNMB), a melanogenesis marker, has been implicated in melanoma progression. This study investigates the expression patterns of GPNMB in SLN metastases and their association with oncological outcomes. We conducted a retrospective analysis of 27 melanoma patients with positive SLNB at Tel Aviv Sourasky Medical Center between 2010 and 2020. Immunohistochemistry was used to assess GPNMB expression in SLN metastases, categorizing patients into two groups based on GPNMB expression patterns: homogeneous (GPNMBho) and margin high (GPNMBmh). Peri-tumoral CD8+ T cell infiltration was also evaluated. Clinical outcomes, including melanoma-specific survival (MSS) and disease-free survival (DFS), were analyzed. GPNMB expression in SLN metastases displayed two distinct patterns: uniform (GPNMBho) and high at the tumor margins (GPNMBmh). Patients in the GPNMBmh group had significantly more peri-tumoral CD8+ T cells and exhibited improved MSS (127.6, 95% CI: 111.7-143.5 vs 79.5, 95% CI: 48.2-110.9 months, P = 0.018) and DFS (107.5, 95% CI: 79-135.8 vs 38, 95% CI: 15.2-60.8 months, P = 0.04) compared to the GPNMBho group. Multivariate analysis confirmed that GPNMB expression pattern and lymph node metastasis size were independent predictors of both MSS and DFS. GPNMB expression patterns in SLN metastases are strongly associated with long-term oncological outcomes in melanoma patients. The GPNMBmh pattern, characterized by higher margin expression and increased CD8+ infiltration, may serve as a prognostic biomarker for recurrence if validated in larger cohorts.