The heterogeneous behavior of patients with melanoma makes prognostication challenging.,To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed.,This study evaluates the GEP’s prognostic accuracy in an independent cohort of cutaneous melanoma patients.,This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk).,Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria.,Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival.,The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001).,The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each).,GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each).,The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual’s risk for recurrence.,The assay identified 70% of stage I and II patients who ultimately developed distant metastasis.,Its role in consideration of patients for adjuvant therapy should be examined prospectively.,The online version of this article (10.1186/s12885-018-4016-3) contains supplementary material, which is available to authorized users.
Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma.,This study aimed to identify prognostic factors in patients with distant metastasis.,We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan-Meier survival probabilities and multivariate Cox hazard regression analysis.,Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses.,Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival.,Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis.,This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%).,The serum markers LDH and S100B were both found to be prognostic factors in melanoma patients with distant metastasis.,Furthermore, complete metastasectomy had an independent favourable prognostic impact in particular for the patient subgroup with normal LDH and S100B values.