Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma

Loren E. Clarke, B. M. Warf, Darl D. Flake, Anne Renee Hartman, Steven Tahan, Christopher R. Shea, Pedram Gerami, Jane Messina, Scott R. Florell, Richard J. Wenstrup, Kristen Rushton, Kirstin M. Roundy, Colleen Rock, Benjamin Roa, Kathryn A. Kolquist, Alexander Gutin, Steven Billings, Sancy Leachman

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)244-252
Number of pages9
JournalJournal of cutaneous pathology
Issue number4
StatePublished - Apr 1 2015


  • melanoma
  • molecular diagnositcs
  • pathology
  • real time PCR
  • validation studies

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Dermatology


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