Unravelling the link between mismatch repair protein deficiency and immune checkpoint markers – programmed death Ligand 1 and Galectin-9 expression in malignant melanoma

Abstract

Malignant melanoma is an aggressive skin cancer, with immune evasion mechanisms contributing to tumour progression. This study evaluated the relationship between mismatch repair (MMR) protein loss and the expression of immune checkpoint molecules programmed death ligand 1 (PD-L1) and galectin-9. Ninety melanoma cases (60 primary, 30 metastatic) were analysed by immunohistochemistry for MMR proteins, PD-L1, and galectin-9. Associations with clinicopathological features and overall survival (OS) were assessed. Mismatch repair protein loss occurred in 5% of primary and 16.7% of metastatic melanomas (p = 0.015). Programmed death ligand 1 was positive in 18.8% of cases, with higher expression in metastatic tumours, but this was not statistically significant (p = 0.106). All PD-L1 positive tumours retained MMR proteins. Galectin-9 expression tended to be higher in tumours with MMR loss and in PD-L1-positive cases, but correlations were not significant. Median OS was 26.0 months, and no variable significantly affected survival in multivariate analysis. Mismatch repair loss was more frequent in metastatic melanomas and associated with higher galectin-9 expression, whereas PD-L1 showed no clear link with MMR status. None of the associations reached statistical significance, emphasising the descriptive and exploratory nature of the study. These findings outline biomarker expression patterns in melanoma and support further investigation in larger cohorts, including patients treated with immune checkpoint inhibitors, to clarify their potential clinical relevance.