In:
British Journal of Dermatology, Oxford University Press (OUP), ( 2023-11-25)
Kurzfassung:
Combined loss of the autophagy-regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoural epidermis of stage I melanomas can identify tumour subsets at low risk of metastasis. Objectives The aim of the present study was to validate the combined loss of peritumoural 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 peritumoural AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of non-ulcerated 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 compared to 81.7% in the AMBLor at-risk group (multivariate log-rank, P & lt; 0.001), and a negative predictive value (NPV) of 96%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low risk group compared to 78.3% in the at-risk group (multivariate log-rank, P & lt; 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), with an overall NPV of 96.5%. Conclusions These data provide further evidence validating AMBLor as a prognostic biomarker to identify non-ulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.
Materialart:
Online-Ressource
ISSN:
0007-0963
,
1365-2133
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2023
ZDB Id:
2004086-6
