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Melanocortin-1 receptor variants and telomerase reverse transcriptase promoter mutations as prognostic biomarkers in stage IIB-IIC melanoma

Stage IIB-IIC cutaneous melanomas carry a substantial risk of recurrence and disease-related mortality despite complete surgical excision, highlighting the need for reliable prognostic biomarkers. We retrospectively analyzed 153 patients with stage IIB-IIC cutaneous melanoma who underwent surgery at...

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Main Authors: Scala, Marcella (Author) , Lorente-Estellés, David (Author) , Liguori, Luigi (Author) , Juan-Fita, María José (Author) , De Nicola, Emanuela (Author) , García-Casado, Zaida (Author) , Traves, Victor (Author) , Moro, Ruggero (Author) , Requena, Celia (Author) , Kumar, Rajiv (Author) , Formisano, Luigi (Author) , Nagore, Eduardo (Author)
Format: Article (Journal)
Language:English
Published: June 2026
In: Melanoma research
Year: 2026, Volume: 36, Issue: 4, Pages: 286-295
ISSN:1473-5636
DOI:10.1097/CMR.0000000000001113
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/CMR.0000000000001113
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Author Notes:Marcella Scala, David Lorente-Estellés, Luigi Liguori, María José Juan-Fita, Emanuela De Nicola, Zaida García-Casado, Victor Traves, Ruggero Moro, Celia Requena, Rajiv Kumar, Luigi Formisano, Eduardo Nagore
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Summary:Stage IIB-IIC cutaneous melanomas carry a substantial risk of recurrence and disease-related mortality despite complete surgical excision, highlighting the need for reliable prognostic biomarkers. We retrospectively analyzed 153 patients with stage IIB-IIC cutaneous melanoma who underwent surgery at the Instituto Valenciano de Oncología between May 2000 and August 2024. Recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS) were estimated using Kaplan-Meier methods. Associations between clinicopathologic and molecular characteristics and survival outcomes were assessed by log-rank test and Cox proportional hazards models. At a median follow-up of 81.6 months, median RFS, DFS, and OS were 43, 31, and 50 months, respectively. In univariate analyses, both telomerase reverse transcriptase (TERT) promoter mutations [hazard ratio = 0.38, 95% confidence interval (CI) = 0.18-0.8, P  = 0.008] and the absence of melanocortin-1 receptor (MC1R) variants (hazard ratio = 0.38, 95% CI = 0.16-0.91, P  = 0.024) were significantly associated with RFS. In multivariate analyses, only TERT promoter mutations remained an independent predictor of both RFS (hazard ratio = 0.44, 95% CI = 0.20-0.96, P  = 0.038) and DFS (hazard ratio = 0.47, 95% CI = 0.24-0.93, P  = 0.030). Patients harboring TERT promoter mutations exhibited significantly poorer survival outcomes compared with those with wild-type TERT promoter status. Combined analysis supported the contrasting prognostic roles of TERT and MC1R. Our findings identify TERT promoter mutations as an independent prognostic factor and suggest a potential protective role of MC1R variants in stage IIB-IIC cutaneous melanoma.
Item Description:Gesehen am 16.09.2026
Physical Description:Online Resource
ISSN:1473-5636
DOI:10.1097/CMR.0000000000001113

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