Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients

Abstract

BackgroundThe DecisionDx-Melanoma test provides prognostic information for patients with cutaneous melanoma (CM). Using formalin-fixed paraffin-embedded primary tumor tissue, the RT-PCR-based test classifies patients into a low- (Class 1) or high-risk (Class 2) category for recurrence based on expression of 31 genes. The current study was designed to assess the analytical validity of this test.MethodsInter-assay, inter-instrument, and inter-operator studies were performed to evaluate reliability of the 31-gene expression test results, sample stability and reagent stability. From March 2013 through June 2016, the gene expression test was performed on 8244 CM tumors. De-identified data from Pathology Reports were used to assess technical success.ResultsRobust sample and reagent stability was observed. Inter-assay concordance on 168 specimens run on 2 consecutive days was 99% and matched probability scores were significantly correlated (R2 = 0.96). Inter-instrument concordance was 95%, and probability scores had a correlation R2 of 0.99 (p < 0.001). From 8244 CM specimens submitted since 2013, 85% (7023) fulfilled pre-specified tumor content parameters. In these samples with sufficient tumor requirements, the technical success of the test was 98%.ConclusionDecisionDx-Melanoma is a robust gene expression profile test that demonstrates strong reproducibility between experiments and has high technical reliability on clinical samples.Electronic supplementary materialThe online version of this article (10.1186/s13000-018-0690-3) contains supplementary material, which is available to authorized users.

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

“…The formalin-fixed paraffin-embedded primary cutaneous melanoma tissue was analysed with the 31-GEP test (DecisionDx-Melanoma, Castle Biosciences, Inc). 15,25 Moreover, the RT-PCR-based test classifies patients into a low-risk (Class 1) or high-risk (Class 2) category for recurrence, as previously reported and validated. 15 Disease-free survival (DFS) was defined as the period of time in months from the date of diagnosis to the date of relapse.…”

“…P-values <0.05 were considered significant. Statistical analyses were performed using SPSS v. 25.0 (IBM Corp., Armonk, NY, USA), and Cox regression analysis was performed using R studio (R Studio Team (2015). RStudio: Integrated Development for R. RStudio, Inc., Boston, MA, USA).…”

“…In all patients, tumour specimens were obtained from the hospital biobank. The formalin‐fixed paraffin‐embedded primary cutaneous melanoma tissue was analysed with the 31‐GEP test (DecisionDx‐Melanoma, Castle Biosciences, Inc) . Moreover, the RT‐PCR‐based test classifies patients into a low‐risk (Class 1) or high‐risk (Class 2) category for recurrence, as previously reported and validated …”

Identification of risk in cutaneous melanoma patients: Prognostic and predictive markers

“…Genes included in the 31‐GEP were distilled from a comparative review of multimarker studies performed between 2000 and 2011, from which over 150 genes associated with recurrence were identified . The test includes three control genes and 28 prognostic genes that have been validated in three multicenter retrospective cohorts, two prospective studies, and an analytic analysis that reported robust reproducibility of the test (98% technical success rate in 8244 clinically tested specimens) . Unlike the tests described above, the 31‐GEP uses radial basis machine (RBM) pattern recognition modeling to compare the GEP of a test sample to a training set containing 164 melanoma tumors with known outcomes.…”

Development and Initial Validation of Calculated Tumor Area as a Prognostic Tool in Cutaneous Malignant Melanoma

“…4,5 Its prognostic value is likely to be associated with its surrogacy for tumor size, which correlates with risk of metastasis, as exemplified by breast cancer. 6 At present, active pursuit of molecular prognostic biomarkers such as the DecisionDx-Melanoma test (Castle Biosciences, Inc) 7,8 have the advantage of a rational basis founded on tumor biology, but these tests can be expensive and require specialist equipment or laborious protocols. Therefore, we focused on microscopic biomarkers requiring no more than the hematoxylin-eosin (H&E)-stained sections used for diagnosis.…”