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Validation of Epidermal AMBRA1 and Loricrin (AMBLor) as a prognostic biomarker for non-ulcerated AJCC stage I/II cutaneous melanoma

Ewen, Tom, Husain, Akhtar, Stefanos, Niki, Barrett, Paul, Jones, Claire, Ness, Tom, Long, Anna, Horswell, Stuart, Bosomworth, Helen, Lowenstein, Joe, Richardson, Grant, Swan, David, McConnell, Ashleigh, Rose, Aidan, Andrew, Tom, Reynolds, Nick, Malvehy, Josep, Carrera, Christina, Also, Llucia, Mailer, Sonia, Helm, Thomas, Ding, Liang, Bogner, Paul, Podlipnik, Sebastian, Puig, Susana, McArthur, Grant, Paragh, Gyorgy, Labus, Marie, Sloan, Philip, Armstrong, Jane and Lovat, Penny (2023) Validation of Epidermal AMBRA1 and Loricrin (AMBLor) as a prognostic biomarker for non-ulcerated AJCC stage I/II cutaneous melanoma. British Journal of Dermatology. ISSN 0007-0963

Item Type: Article

Abstract

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.

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Depositing User: Jane Armstrong

Identifiers

Item ID: 17239
Identification Number: https://doi.org/10.1093/bjd/ljad459
ISSN: 0007-0963
URI: http://sure.sunderland.ac.uk/id/eprint/17239
Official URL: https://academic.oup.com/bjd/advance-article/doi/1...

Users with ORCIDS

ORCID for Jane Armstrong: ORCID iD orcid.org/0000-0002-5822-0597

Catalogue record

Date Deposited: 23 Jan 2024 15:27
Last Modified: 23 Jan 2024 15:30

Contributors

Author: Jane Armstrong ORCID iD
Author: Tom Ewen
Author: Akhtar Husain
Author: Niki Stefanos
Author: Paul Barrett
Author: Claire Jones
Author: Tom Ness
Author: Anna Long
Author: Stuart Horswell
Author: Helen Bosomworth
Author: Joe Lowenstein
Author: Grant Richardson
Author: David Swan
Author: Ashleigh McConnell
Author: Aidan Rose
Author: Tom Andrew
Author: Nick Reynolds
Author: Josep Malvehy
Author: Christina Carrera
Author: Llucia Also
Author: Sonia Mailer
Author: Thomas Helm
Author: Liang Ding
Author: Paul Bogner
Author: Sebastian Podlipnik
Author: Susana Puig
Author: Grant McArthur
Author: Gyorgy Paragh
Author: Marie Labus
Author: Philip Sloan
Author: Penny Lovat

University Divisions

Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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