Abstract

Cutaneous melanoma continues to increase globally with AJCC Stage I/II tumours representing 91% of all diagnoses. The inability of current AJCC staging criteria to distinguish genuinely low risk patient subsets emphasises the acute need for credible biomarkers based on personalised risk. We have previously identified the combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas as a prognostic biomarker and valuable pre SLNB test, additionally showing melanoma secretion of TGFβ2 mediates AMBRA1 transcriptional down regulation in the overlying epidermis, subsequent reduction in epidermal integrity and tumour ulceration. In the present study we aimed to evaluate the potential for AMBLor as a prognostic biomarker for both non-ulcerated AJCC stage I and II cutaneous melanoma. AMBLor expression was analysed and correlated with >10 year clinical follow in a retrospective cohort of 548 non-ulcerated AJCC (8th edition) stage I (447) and II (101) cutaneous melanomas from the Roswell Park Cancer Centre, USA and Peter McCallum Cancer Centre, Australia using a clinically validated automated IHC assay for FFPE tissue. Each cohort was powered to represent rates of 10 or up to 20% metastasis for stage I or II disease with binary scoring and concordance undertaken by 4 pathologists blinded to clinical outcome. Results revealed retention of AMBLor correlated with significantly increased disease free survival of 96% compared to 88% for patients with stage I/II melanomas in which AMBLor was lost (P< 0.001; HR 0.28, 95% CI 0.15-0.53, NPV 96.1%, assay sensitivity 93% Collectively these data suggest AMBLor as a marker to identify genuinely low risk subsets of non-ulcerated AJCC stage I/II melanomas, the inclusion of which into clinical diagnostic pathways provides additional prognostic information over and above AJCC staging to tailor appropriate clinical follow up and improve patient anxiety.

Financial Disclosure:

Speaker	Ineligible Company	Affiliation/Relationship	Ongoing/Ended	Role
Phil Sloan, BDS, PhD, FRCPath	AMLo Biosciences Ltd	Chief Pathologist	Ongoing	Oral Abstract Presenter