An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

Abstract

BACKGROUNDRecently, a 23‐gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.METHODSA set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis.RESULTSThe gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%.CONCLUSIONSThese results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617–628. © 2016 American Cancer Society.

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

“…Consensus ratings in most of the clinical scenarios using qRT‐PCR were of “appropriateness uncertain” with the exception being those cases where a diagnosis can be made on histologic grounds. While validation studies and studies exploring unequivocal cases had been published when the AUC process began, only one study was available exploring the test in ambiguous lesions at the time of rating. In addition, the possibility of limited clinical experience with the test may have played a role in the rating result.…”

Evidence behind the use of molecular tests in melanocytic lesions and practice patterns of these tests by dermatopathologists

“…The two validation studies suggest qRT-PCR has a sensitivity of 90% to 91.5% and a specificity of 91% to 92.5% for melanoma. 25,50 In one study, there was 97% and 83% concordance with histology for FISH and qRT-PCR in a group of unequivocal melanocytic lesions resulting in a sensitivity and specificity of 93% and 100% for FISH and 62% and 95% for qRT-PCR. The intertest agreement was found to be 80%.…”

A machine-learning classifier trained with microRNA ratios to distinguish melanomas from nevi

“…Despite the limited size of the training set, the sensitivity and specificity of the MiRTM for validation sets thresholded on the discovery cohort was 0.83 and 0.71-0.83. This performance of the MiRTM is comparable to other molecular tests for distinguishing benign melanocytic nevi from melanoma, including chromosomal analysis by fluorescence in situ hybridization (sensitivity 0.72-1.00, specificity 0.90-1.00) (Gerami et al 2010;Ferrara and De Vanna 2016) and myPath Melanoma gene expression profiling (sensitivity 0.63-0.90, specificity 0.88-0.93) (Clarke et al 2017;Minca et al 2016). The MiRTM does not perform as well as chromosomal analysis by array comparative genomic hybridization (aCGH, sensitivity 0.92-0.96, specificity 0.87-1.00) (Bastian et al 2003;Wang et al 2013).…”