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Lookup NU author(s): Dr Robert EllisORCiD, Dr Diana Tang, Dr Batoul Nasr, Alison Greenwood, Dr Ashleigh McConnell, Maria Anagnostou, Madona Elias, Dr Stamatina Verykiou, Dr Dalvir Bajwa, Dr Tom EwenORCiD, Professor Nick ReynoldsORCiD, Dr Graeme Watson, Dr Jane Armstrong, Dr Joy AllenORCiD, Dr Marie Labus, Professor Penny Lovat
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background - The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high‐risk stage I tumour subsets. Objectives - To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma.Methods - Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas.Results - Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7‐year disease‐free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi‐quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low‐risk group (n = 239) vs. 85·4% in the AMLo high‐risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69–9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93–9·56; P = 0·068) in stage IB patients.Conclusions - Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high‐risk tumour subsets independently of Breslow depth.
Author(s): Ellis R, Tang D, Nasr B, ClinRes M, Greenwood A, McConnell A, Anagnostou ME, Elias M, Verykiou S, Bajwa D, Ewen T, Reynolds NJ, Barrett P, Carling E, Watson G, Armstrong J, Allen AJ, Horswell S, Labus M, Lovat PE
Publication type: Article
Publication status: Published
Journal: British Journal of Dermatology
Year: 2020
Volume: 182
Issue: 1
Pages: 156-165
Print publication date: 01/01/2020
Online publication date: 06/05/2019
Acceptance date: 24/04/2019
Date deposited: 30/04/2019
ISSN (print): 0007-0963
ISSN (electronic): 1365-2133
Publisher: Wiley
URL: https://doi.org/10.1111/bjd.18086
DOI: 10.1111/bjd.18086
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