The objective of our study was to compare the five different scoring methods of tumor-infiltrating lymphocytes (TILs) assessment in a group of 213 cases of superficial spreading and nodular melanoma. The scoring methods include (a) Clark scoring; (b) Melanoma Institute Australia system; (c) scoring system used in the study of Saldanha et al.; (d) scoring system used in the TCGA study and modified by Park et al.; and (e) the system recently proposed by the "International Immuno-Oncology Biomarker Working Group" for TILs scoring in all solid tumors. Prediction of survival with three main outcomes-disease-specific-free survival, local recurrence-free survival, and distant metastasis-free survival-was evaluated. The prognostic value of TILs showed statistical significance in univariate analysis regarding all three of the outcomes only for three of the five evaluated methods; the Clark scoring, the Melanoma Institute Australia system, and the system proposed by the "International Immuno-Oncology Biomarker Working Group". However, in multivariate analysis with covariants including Breslow thickness, type of melanoma, location, sex, and age, we did not find TILs to be an independent prognostic factor.

Department of Dermatology and Venereology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

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A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants