Abstract
9573 Background: Cutaneous melanoma incidence continue to increase, with a particular increase in the number of patients diagnosed with thin, < 1mm tumours with reduced probability of recurrence-free survival. The inability of current AJCC staging criteria to identify genuinely low risk subsets of patients with AJCC stage I/II tumours thus emphasises the acute need for credible prognostic biomarkers to stratify patient follow-up based on personalised risk. The combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas has recently been identified as a prognostic biomarker and valuable pre SLNB test. The aim of the present study was to evaluate the potential for AMBLor as a prognostic biomarker for both AJCC stage I and II non-ulcerated melanoma. Methods: Prospective analysis of AMBLor was performed in two independent retrospective cohorts of non-ulcerated AJCC (8th edition) stage I and II cutaneous melanomas derived from the USA and Australia (discovery cohort) and Spain and the UK (Validation cohort) following validated automated immune-histological staining and binary scoring analysis to define at risk vs low risk subgroups. Each cohort was powered to represent rates of 10% or up to 20% metastasis for stage I or stage II disease respectively. Results: Data revealed retention of AMBLor in the discovery cohort of 541 melanomas correlated with significantly increased recurrence-free survival (RFS) of 96% compared to 87% for patients with stage I/II melanomas in which AMBLor was lost (P = 0.06; HR 3.6, 95% CI 1.99-6.84, NPV 96%). Subsequent AMBLor analysis in the validation cohort of 303 tumours, further confirmed retention of AMBLor was associated with increased RFS of 98% compared to 81% for patients with stage I/II tumours in which AMBLor was lost (P = 0.01; HR 8.16, 95% CI 3.68-18.07). Conclusions: Collectively data from this multi-international study confirm AMBLor as a prognostic biomarker marker able to identify genuinely low risk subsets of AJCC stage I/II melanomas. Inclusion of AMBLor into clinical melanoma management may therefore aid stratification of patient follow up, enable significant savings on healthcare resources and improve patient anxiety.
Published Version
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