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Lookup NU author(s): Dr Tom EwenORCiD, 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.
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
URL: https://doi.org/10.1093/bjd/ljad459
DOI: 10.1093/bjd/ljad459
Data Access Statement: The data underlying this article will be shared upon reasonable request to the corresponding author
PubMed id: 38006317
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