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

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

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;
Details: Publication Year 2024-03-15,Volume 190,Issue #4,Page 549-558
Journal Title: British Journal of Dermatology
Publication Type: Research 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.
Publisher: Oxford University Press
Keywords: Humans; United States; *Melanoma/pathology; *Skin Neoplasms; Prognosis; Neoplasm Recurrence, Local/pathology; Epidermis/metabolism; Biomarkers; Neoplasm Staging; Adaptor Proteins, Signal Transducing/metabolism; *Membrane Proteins
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1093/bjd/ljad459
Open Access at Publisher's Site: https://doi.org/10.1093/bjd/ljad459
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-04-02 04:13:37

Last Modified: 2024-04-02 04:13:52