Development and Validation of a Diagnostic 35-Gene Expression Profile Test for Ambiguous or Difficult-To-Diagnose Suspicious Pigmented Skin Lesions

Sarah I. Estrada, Jeffrey B. Shackelton, Nathan J. Cleaver, Natalie D. Depcik-Smith, Clay J. Cockerell, Stephen N. Lencioni, Howard L. Martin, Jeffrey Wilkinson, Lauren Meldi Sholl, Michael D. Berg, Brooke H. Russell, Olga Zolochevska, Kyle R. Covington, Aaron S. Farberg, Matthew S. Goldberg, Pedram Gerami, Gregory A. Hosler

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Purpose: A clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. While histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. The development and validation of a 35-gene expression profile (35-GEP) test that accurately differentiates benign and malignant pigmented lesions is described. Methods: Lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. Diagnostic utility of 76 genes was assessed with quantitative RT-PCR; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. To reflect the complex biology of melanocytic neoplasia, the 35-GEP test was developed to include an intermediate-risk zone. Results: Validation of the 35-GEP was performed in an independent set of 273 benign and 230 malignant lesions. The test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk. Conclusions: The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. A test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients.

Original languageEnglish
Pages (from-to)506-522
Number of pages17
JournalSKIN: Journal of Cutaneous Medicine
Volume4
Issue number6
DOIs
StatePublished - 15 Nov 2020

Keywords

  • 35-GEP
  • benign nevi
  • diagnostic test
  • melanoma
  • validation

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