Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients

Abstract

BackgroundThe 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.MethodsThis 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.ResultsThe 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4016-3) contains supplementary material, which is available to authorized users.

Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities

“…The test assesses the expression of three control genes, four genes with proven prognostic utility for UMs [31] and 24 genes previously reported to be differentially expressed in metastatic compared to primary tumours [32][33][34][35][36][37][38]. The performance of this test has been evaluated in several retrospective [30,39,40] as well as prospective validation studies [41,42] and has been shown to enhance current prognostic accuracy in particular through identifying clinically and pathologically sentinel lymph node (SLN)-negative patients with high-risk of metastases. However, although there is great promise in reproducibility and clinical validity, the clinical utility for the 31-GEP test on clinical decision-making is still incompletely defined, and will require evidence from further large-scale prospective multi-institutional registry studies before it can be considered for inclusion in any national or professional association guideline recommendations.…”

Early outcome of a 31‐gene expression profile test in 86 AJCC stage IB‐II melanoma patients. A prospective multicentre cohort study

“…14 Recently, new prognostic tests based on genetic profiling signatures have been developed to better identify those patients who are at a higher risk of developing metastasis leading to death. [15][16][17][18][19][20] A gene expression profile (GEP) test (DecisionDx-Melanoma, Castle Biosciences, Inc., Friendswood, TX, USA) evaluates 31 genes of primary cutaneous melanoma tumours and based on the expression of these genes (genetic signature) it classifies patients into two groups of risk of relapse, low (class 1) or high (class 2). This test has been validated in several historical cohorts showing that its prognostic ability is independent from the clinical and pathological features of the tumour.…”

“…This test has been validated in several historical cohorts showing that its prognostic ability is independent from the clinical and pathological features of the tumour. [15][16][17][18][19][20][21][22][23][24] However, this test has never before been evaluated in a prospective multicentre cohort.…”

Performance of a 31‐gene expression profile test in cutaneous melanomas of the head and neck

“…Gene expression profile (GEP) class assignment was performed using the commercially available 31-GEP test (DecisionDx-Melanoma) available from Castle Biosciences, Inc. (Friendswood, Texas), the development and validation of which has been previously described. [17][18][19] This clinical test reports a class probability assignment of either Class 1 (low risk) or Class 2 (high risk), as well as a reduced confidence assignment with "A" reflecting a better and "B" reflecting worse outcomes resulting in assignments of Class 1A, 1B, 2A, and 2B. The melanoma cases included in this study are exclusive of the training set used in the test's algorithm.…”