title: Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes.
abstract: Background:Histopathologic examination alone can be inadequate for diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature was clinically validated as an ancillary diagnostic test to differentiate benign nevi from melanoma. The current study assessed the performance of this test in an independent cohort of melanocytic lesions against clinically proven outcomes.Methods:Archival tissue from primary cutaneous melanomas and melanocytic nevi was obtained from four independent institutions and tested with the gene signature. Cases were selected according to pre-defined clinical outcome measures. Malignant lesions were defined as stage I-III primary cutaneous melanomas that produced distant metastases (metastatic to sites other than proximal sentinel lymph node(s)) following diagnosis of the primary lesion. Melanomas that were metastatic at the time of diagnosis, all re-excisions, and lesions with <10% tumor volume were excluded. Benign lesions were defined as cutaneous melanocytic lesions with no adverse long-term events reported.Results:Of 239 submitted samples, 182 met inclusion criteria and produced a valid gene expression result. This included 99 primary cutaneous melanomas with proven distant metastases and 83 melanocytic nevi. Median time to melanoma metastasis was 18 months. Median follow-up time for nevi was 74.9 months. The gene expression score differentiated melanoma from nevi with a sensitivity of 93.8% and a specificity of 96.2%.Conclusions:The results of gene expression testing closely correlate with long-term clinical outcomes of patients with melanocytic neoplasms.Impact:Collectively, this provides strong evidence that the gene signature adds valuable adjunctive information to aid in the accurate diagnosis of melanoma.Cancer Epidemiol Biomarkers Prev; 26(7); 1107-13. ©2017 AACR.
authors.affiliation: The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Ko
authors.affiliation: University of Nottingham, Nottingham, United Kingdom.
authors.forename: Balwir
authors.initials: B
authors.lastname: Matharoo-Ball
authors.affiliation: The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Billings
authors.affiliation: University of Nottingham, Nottingham, United Kingdom.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Thomson
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Tang
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Kavita Y
authors.initials: KY
authors.lastname: Sarin
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Emily
authors.initials: E
authors.lastname: Cai
authors.affiliation: Stanford University, Stanford, California.
authors.forename: Jinah
authors.initials: J
authors.lastname: Kim
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Colleen
authors.initials: C
authors.lastname: Rock
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Hillary Z
authors.initials: HZ
authors.lastname: Kimbrell
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Darl D
authors.initials: DD
authors.lastname: Flake
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: M Bryan
authors.initials: MB
authors.lastname: Warf
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nelson
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Thaylon
authors.initials: T
authors.lastname: Davis
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Catherine
authors.initials: C
authors.lastname: Miller
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Kristen
authors.initials: K
authors.lastname: Rushton
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Anne-Renee
authors.initials: AR
authors.lastname: Hartman
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wenstrup
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, Utah. lclarke@myriad.com.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Clarke
mesh_terms: D000328:Adult; D000368:Aged; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology; D059467:Transcriptome