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Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma
Author(s) -
Clarke Loren E.,
Warf M.B.,
Flake Darl D.,
Hartman AnneRenee,
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
Publication year - 2015
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.12475
Subject(s) - pathology , melanoma , medicine , gene signature , anatomical pathology , gene expression profiling , gene expression , gene , immunohistochemistry , biology , cancer research , biochemistry
Background 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. Methods 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. Results 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%. Conclusions 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.