Genomic Atypia to Enrich Melanoma Positivity in Biopsied Lesions: Gene Expression and Pathology Findings From a Large U.S. Registry Study

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Brook Brouha
Laura Ferris
Maral Skelsey
Gary Peck
Jim Rock
Anh Nguyen
Zuxu Yao
Michael Howell
Burkhard Jansen
Clay Cockerell


Melanoma, Biomarker, Rule-out Test, Clinical Utility, Non-Invasive, Gene Expression, Pigmented Lesion


Importance: Melanoma is diagnosed in approximately 200,000 people within the US each year and is responsible for more than 6,850 deaths. Currently, clinical suspicion guides biopsy decisions and melanoma is confirmed in approximately 4% of biopsied lesions. A non-invasive two-gene expression test (2-GEP) was shown to enhance the physical exam by evaluating genomic atypia to guide biopsy decisions. This study examines the corresponding histopathology of real-world 2-GEP-positive cases.

Methods: Cutaneous lesions suspicious for melanoma (n=3,418) were 2-GEP tested by 90 licensed clinicians in real-world practice. 2-GEP-positive lesions (genomically atypical as indicated by the detection of LINC and/or PRAME) were biopsied in 316 out of 324 (97.5%) cases and 313 pathology reports were available for analysis.

Results: Biopsied 2-GEP-positive lesions were separated into diagnostic subgroups based on corresponding pathology reports. The prevalence of melanoma in biopsies of 2-GEP-positive lesions was 18.7%. Gene expression of both LINC and PRAME was present in ever-increasing percentages of melanocytic lesions as pathology reports demonstrated increasing levels of atypia. Notably, 47.5% of the histopathologically-confirmed melanomas demonstrated this double positive genomic signature while 23.7% were single-positive for LINC and 28.8% were single-positive for PRAME. 

Discussion: These data show that biopsied 2-GEP-positive lesions are enriched almost five-fold for advanced histopathologic features compared to those biopsied based solely on visual assessment criteria. The close correlation between genomic atypia and atypical pathology should be considered when planning treatment of a 2-GEP-positive lesion.  Consideration of genomic atypia may be a superior approach to guide biopsy decisions and manage pigmented lesions.


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