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.
Subject(s)
Melanoma , Membrane Proteins , Skin Neoplasms , Humans , United States , Melanoma/pathology , Prognosis , Neoplasm Recurrence, Local/pathology , Epidermis/metabolism , Biomarkers , Neoplasm Staging , Adaptor Proteins, Signal Transducing/metabolismSubject(s)
Skin Neoplasms , Thigh , Humans , Thigh/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Lower Extremity/pathologySubject(s)
Scleroderma, Localized , Scleroderma, Systemic , Humans , Adult , Scleroderma, Systemic/diagnosisSubject(s)
Dysplastic Nevus Syndrome , Skin Neoplasms , Dermatologists , Humans , Plant Leaves , Surveys and Questionnaires , United StatesSubject(s)
Heuristics , Nevus, Epithelioid and Spindle Cell , Diagnosis, Differential , Hemangioma , Humans , Melanoma , Skin NeoplasmsABSTRACT
This report details an acral melanoma in-situ on theright plantar foot that was successfully treated withMohs micrographic surgery and secondary intentionwound healing.
