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

Autor:	Ewen T; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Husain A; Novo Path and Cellular Pathology., Stefanos N; Pathology, Addenbrookes Hospital, Cambridge University NHS Trust, Cambridge, UK., Barrett P; Pathology, University Hospitals of North Durham, Durham, UK., Jones C; Novo Path and Cellular Pathology., Ness T; Novo Path and Cellular Pathology., Long A; Novo Path and Cellular Pathology., Horswell S; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; Francis Crick Institute, London, UK., Bosomworth H; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Lowenstein J; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; AMLo Biosciences, Newcastle upon Tyne, UK., Richardson G; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; AMLo Biosciences, Newcastle upon Tyne, UK., Swan D; AMLo Biosciences, Newcastle upon Tyne, UK.; Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK., McConnell A; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; AMLo Biosciences, Newcastle upon Tyne, UK., Rose A; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Andrew T; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Reynolds N; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK., Malvehy J; Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain., Carrera C; Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain., Alos L; Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain., Mailer S; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia., Helm T; Division of Dermatology, Buffalo Medical Group, Williamsville, NY, USA.; Department of Dermatology, Penn State Hershey, Hershey, Pennsylvania, USA., Ding L; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Bogner P; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.; Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Podlipnik S; Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain., Puig S; Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain., McArthur GA; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia., Paragh G; Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Labus M; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; AMLo Biosciences, Newcastle upon Tyne, UK., Sloan P; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; Novo Path and Cellular Pathology.; AMLo Biosciences, Newcastle upon Tyne, UK., Armstrong JL; AMLo Biosciences, Newcastle upon Tyne, UK.; Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK., Lovat PE; Translation and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; AMLo Biosciences, Newcastle upon Tyne, UK.
Jazyk:	angličtina
Zdroj:	The British journal of dermatology [Br J Dermatol] 2024 Mar 15; Vol. 190 (4), pp. 549-558.
DOI:	10.1093/bjd/ljad459
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)
Databáze:	MEDLINE
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