Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

BackgroundCurrent staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value identifying patients who will experience metastasis.ObjectiveTo develop and validate a gene expression profile (GEP) test predicting risk metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.MethodsArchival formalin-fixed paraffin-embedded primary tissue clinicopathologic data (n = 586) were collected from 23 independent centers prospectively designed study. A GEP signature was developed using discovery cohort 202) validated separate, nonoverlapping, 324).ResultsA prognostic 40-GEP validated, stratifying into classes based on risk: class 1 (low risk), 2A (high 2B (highest risk). For validation cohort, 3-year metastasis-free survival rates 91.4%, 80.6%, 44.0%, respectively. 60% achieved highest-risk group (class 2B), an improvement over systems, negative value, sensitivity, specificity comparable to systems.LimitationsPotential understaging cases could affect rate accuracy.ConclusionThe is predictor metastatic that can complement current cSCC. Current metastasis. To management. Archival 324). systems. Potential accuracy. The