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

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

Loren E Clarke  1 , M B Warf, Darl D Flake 2nd, 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
Affiliations

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

Loren E Clarke et al. J Cutan Pathol. 2015 Apr.

Abstract

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.

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Figures

Figure 1
Figure 1
Distribution of the gene expression for the three components in the best performing multivariate signature. A) The individual distribution of RNA expression in benign (grey) and malignant (black) samples in the training cohort for each of the three components. B) Comparison of the RNA expression of each component to each of the other two components in the training cohort. The low correlation (cor) of each comparison is noted.
Figure 2
Figure 2
Receiver operating characteristic (ROC) curve of diagnostic scores in the clinical validation cohort.
Figure 3
Figure 3
Distribution of diagnostic scores in the clinical validation cohort.
See this image and copyright information in PMC

References

    1. Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 1996; 27: 528. - PubMed
    1. McGinnis KS, Lessin SR, Elder DE, et al. Pathology review of cases presenting to a multidisciplinary pigmented lesion clinic. Arch Dermatol 2002; 138: 617. - PubMed
    1. Shoo BA, Sagebiel RW, Kashani‐Sabet M. Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. J Am Acad Dermatol 2010; 62: 751. - PubMed
    1. Veenhuizen KC, De Wit PE, Mooi WJ, et al. Quality assessment by expert opinion in melanoma pathology: experience of the pathology panel of the Dutch Melanoma Working Party. J Pathol 1997; 182: 266. - PubMed
    1. Barnhill RL, Argenyi ZB, From L, et al. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol 1999; 30: 513. - PubMed

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