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

J Cutan Pathol. 2015 Apr;42(4):244-52. doi: 10.1111/cup.12475. Epub 2015 Apr 13.


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.

Keywords: melanoma; molecular diagnositcs; pathology; real time PCR; validation studies.

Publication types

  • Validation Study

MeSH terms

  • Cohort Studies
  • Diagnosis, Differential
  • Humans
  • Melanocytes / pathology
  • Melanoma / diagnosis*
  • Melanoma / genetics*
  • Melanoma / pathology
  • Nevus, Pigmented / diagnosis*
  • Nevus, Pigmented / genetics*
  • Nevus, Pigmented / pathology
  • Paraffin Embedding
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Tissue Fixation
  • Transcriptome

Supplementary concepts

  • Melanoma, Cutaneous Malignant