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
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Abstract
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.
| Item Type: | Article |
|---|---|
| Depositing User: | Jane Armstrong |
| URI: | https://sure.sunderland.ac.uk/id/eprint/17239 |
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