Epidermal AMBRA1 and Loricrin; a paradigm shift in the prognostication and stratification of AJCC stage I melanomas

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

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
Subjects: Sciences > Biomedical Sciences
Divisions: Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences
Related URLs:
Depositing User: Jane Armstrong
Date Deposited: 30 May 2019 11:07
Last Modified: 06 May 2020 02:38
URI: http://sure.sunderland.ac.uk/id/eprint/10802
ORCID for Jane Armstrong: ORCID iD orcid.org/0000-0002-5822-0597

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