Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. (13th April 2015)

• Record Type: Journal Article
• Authors: Clarke, Loren E.; Warf, B.M.; Flake, Darl D.; Hartman, Anne‐Renee; Tahan, Steven; Shea, Christopher R.; Gerami, Pedram; Messina, Jane; Florell, Scott R.; Wenstrup, Richard J.; Rushton, Kristen; Roundy, Kirstin M.; Rock, Colleen; Roa, Benjamin; Kolquist, Kathryn A.; Gutin, Alexander; Billings, Steven; Leachman, Sancy
• Is Part Of: Journal of cutaneous pathology. Volume 42:Number 4(2015:Apr.)
• Page Start: 244
• Page End: 252
• Publication Date: 2015-04-13
• Subjects: Skin -- Diseases -- Periodicals; Dermatology -- Periodicals; 616
• DOI: 10.1111/cup.12475
• Languages: English
• ISSNs: 0303-6987

Abstract

<abstract abstract-type="main" id="cup12475-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cup12475-sec-0001" sec-type="section"> <title>Background</title> <p id="cup12475-para-0001">Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes.</p> </sec> <sec id="cup12475-sec-0002" sec-type="section"> <title>Methods</title> <p id="cup12475-para-0002">Using quantitative reverse‐transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas.</p> </sec> <sec id="cup12475-sec-0003" sec-type="section"> <title>Results</title> <p id="cup12475-para-0003">The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%.</p> </sec> <sec id="cup12475-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="cup12475-para-0004">The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms.</p> </sec> </abstract>