Ellis, R, Tang, D, Nasr, B, Greenwood, A, McConnell, A, Anagnostou, ME, Elias, M, Verykiou, S, Bajwa, D, Ewen, T, Reynolds, NJ, Barrett, P, Carling, E, Watson, G, Armstrong, Jane, Allen, AJ, Horswell, S, Labus, M and Lovat, PE (2019) Epidermal AMBRA1 and Loricrin; a paradigm shift in the prognostication and stratification of AJCC stage I melanomas. British Journal of Dermatology, 182 (1). pp. 156-165. ISSN 1365-2133
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Abstract
Abstract
Summary
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.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Depositing User: | Jane Armstrong |
| URI: | https://sure.sunderland.ac.uk/id/eprint/10802 |
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