Gene Expression Analysis Differentiates Melanomas from Spitz Nevi

May 2018 | Volume 17 | Issue 5 | Editorials | 574 | Copyright © 2018

Burkhard Jansen MD,a Doyle Hansen MD,b Ronald Moy MD,c Maesa Hanhan MS,a and Zuxu Yao PhDa

aDermTech Incorporated, La Jolla, CA bPacific Pathology, San Diego, CA cRodeoDerm Moy Fincher Chips, Beverly Hills, CA

Abstract

Introduction: Pediatric Spitz nevi can pose significant diagnostic challenges to both clinicians and dermatopathologists when the current image-recognition based gold standard is employed. PRAME (preferentially expressed antigen in melanoma) and/or LINC (long intergeneic non-coding RNA 518) gene expression in adult patients in samples obtained non-invasively via adhesive patches differentiates primary melanomas from atypical nevi and other pigmented lesions with a NPV of over 99%, a sensitivity of 91%, and a specificity of 69%, to help clinicians rule out melanoma and the need for surgical biopsies of atypial pigmented lesions with suspicion for melanoma. Surgically obtained melanomas from adult patients show the same gene expression pattern. Methods: In this study, we investigate gene expression patterns of pigmented lesions from FFPE tissue block samples (n=23, 9 male, 14 female patients, median age 12) with a focus on differentiating Spitz nevi from melanomas in children and young adults. Results: PRAME levels were significantly (P less than 0.001) increased based on normalized Ct cycle counts (lower cycle counts indicate higher expression levels) in melanomas (mean Ct 33.83 + 0.54, 95% CI 32.85-34.80) when compared to Spitz nevi (mean Ct 37.21 + 0.98, 95% CI 35.41-39.01) or common nevi (mean Ct 36.94 + 0.80, 95% CI 35.47-38.40), respectively. LINC and 4 control genes showed similar expression levels in all 3 pigmented lesion groups investigated. Clinically and histopathologically complex pediatric Spitz nevi demonstrated gene expression signatures almost identical to gene expression signatures of common pediatric nevi but different from melanomas in children and young adults. Discussion: PRAME but not LINC gene expression can be a valuable molecular aid to differentiate melanomas from Spitz nevi, groups of pigmented lesions that can be particularly difficult to assess in children and young adults. J Drugs Dermatol. 2018;17(5):574-576.

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INTRODUCTION

The accurate assessment of pigmented skin lesions, especially in pediatric settings, is challenging even for pigmented lesion experts.1 The current gold standard of visual assessment paired with histopathology combines two diagnostic modalities that both rely on image and pattern recognition. Inherently, image and pattern recognition are subjective leading to inter and intra-observer discrepancies that may impact how pigmented skin lesions are managed and how plans for treatment and follow-up are devised. Improved diagnostic aides and options are desirable.2-4 Furthermore, it is increasingly recognized that the way a pigmented lesion looks either clinically or under the microscope, is heavily influenced by changes in gene expression patterns that themselves are caused by mutations (in case of pigmented lesions most often acquired in a series of events as a consequence of UV damage).5 Even intricate assessments of morphological features by dermoscopy or confocal microscopy, while without doubt beneficial in the hands of trained experts, are indirect and preceded by changes that may provide superior assessment if easy ways can be found to determine their nature.6 Our team recently validated a molecular dermatology gene expression platform using adhesive patches to non-invasively collect skin samples. LINC (long intergeneic non-coding RNA 518) and/or PRAME (preferentially expressed antigen in melanoma) gene expression in adult patients differentiates primary melanomas from atypical nevi and other pigmented lesions with a NPV of over 99%, a sensitivity of 91% and a specificity of 69% to support clinicians with the management of difficult to assess pigmented lesions.2 Board certified dermatologists and pigmented lesion experts who use LINC/PRAME gene expression to help guide the management of pigmented lesions, surgically biopsy about half as often while missing fewer melanomas.3 The study presented here addresses frequent questions from clinicians who use the test described above and who wanted to know, how Spitz nevi in children and young adults, a group of pigmented skin lesions frequently very similar in morphological appearance to primary cutaneous melanomas and therefore notoriously difficult to assess,1 compare to melanomas and pediatric common nevi at the gene expression level.

MATERIALS AND METHODS

Study Subjects and Tissue Block SamplesThe 23 subjects in this archival study were male (n=9) and female (n=14) patients (median age 12) with histopathologically confirmed pigmented lesions (pediatric melanomas and

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