Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.
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.
Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
Loren E
LE
Clarke
M B
MB
Warf
Darl D
DD
Flake
Anne-Renee
AR
Hartman
Steven
S
Tahan
Christopher R
CR
Shea
Pedram
P
Gerami
Jane
J
Messina
Scott R
SR
Florell
Richard J
RJ
Wenstrup
Kristen
K
Rushton
Kirstin M
KM
Roundy
Colleen
C
Rock
Benjamin
B
Roa
Kathryn A
KA
Kolquist
Alexander
A
Gutin
Steven
S
Billings
Sancy
S
Leachman
D015331:Cohort Studies; D003937:Diagnosis, Differential; D006801:Humans; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009508:Nevus, Pigmented / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D016707:Tissue Fixation; D059467:Transcriptome; D000096142:Cutaneous Malignant Melanoma
melanoma; molecular diagnositcs; pathology; real time PCR; validation studies