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Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma

Lookup NU author(s): Dr Tom Ewen, Stuart Horswell, Dr Helen Bosomworth, Joe Lowenstein, Grant Richardson, Dr David Swan, Dr Ashleigh McConnell, Aidan Rose, Dr Tom Andrew, Professor Nick ReynoldsORCiD, Dr Marie Labus, Professor Philip Sloan, Dr Jane Armstrong, Professor Penny Lovat



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 The Author(s). Published by Oxford University Press on behalf of British Association of Dermatologists.Background: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. Objectives: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. Methods: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. Results: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. Conclusions: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.

Publication metadata

Author(s): Ewen T, Husain A, Stefanos N, Barrett P, Jones C, Ness T, Long A, Horswell S, Bosomworth H, Lowenstein J, Richardson G, Swan D, McConnell A, Rose A, Andrew T, Reynolds N, Malvehy J, Carrera C, Alos L, Mailer S, Helm T, Ding L, Bogner P, Podlipnik S, Puig S, McArthur GA, Paragh G, Labus M, Sloan P, Armstrong JL, Lovat PE

Publication type: Article

Publication status: Published

Journal: British Journal of Dermatology

Year: 2024

Volume: 190

Issue: 4

Pages: 549-558

Print publication date: 04/04/2024

Online publication date: 25/11/2023

Acceptance date: 11/11/2023

Date deposited: 03/04/2024

ISSN (print): 0007-0963

ISSN (electronic): 1365-2133

Publisher: Oxford University Press


DOI: 10.1093/bjd/ljad459

PubMed id: 38006317


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a National Institute for Health and Care Research (NIHR)