Background: Fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) arrays are well-established molecular tests for the analysis of challenging melanocytic lesions. A 23-gene expression signature (GES), marketed as myPath Melanoma, is a recently introduced molecular test that categorizes melanocytic lesions as "benign," "malignant," and "indeterminate." There are few studies on the concordance between FISH, SNP, and GES in the analysis of melanocytic lesions.
Methods: A single-institution retrospective analysis of 61 contiguous cases of challenging melanocytic lesions with molecular analysis by 2 or more techniques. The primary objective was to determine the intertest agreement, which was calculated as percent agreement. A secondary objective was to determine the combined-test performance, that is, the frequency of obtaining a successful test (a test with an abnormal or normal, benign or malignant result) when 2 or more molecular tests were performed.
Results: Of the 61 cases, 58 cases were submitted for analysis using the GES assay, 44 cases were submitted for FISH analysis, and 21 cases were submitted for SNP array analysis. Percent agreement between GES and FISH array was 50.9% (18/34), which improved to 69.7% (18/23) when indeterminate/equivocal results were excluded. Similarly, percent agreement between GES and SNP array was 57.1% (8/14); this improved to 77.8% (7/9) when indeterminate/equivocal results were excluded. In 44% of cases submitted for GES and FISH and in 39% of cases submitted for GES and SNP, one test was successful and the other was not.
Conclusion: For challenging melanocytic lesions, the choice of a molecular test is consequential as the GES assay correlated with FISH and SNP arrays approximately only half of the time. This improved when cases with indeterminate/equivocal results were excluded from the calculations. The combined-test analysis supports the utility of conducting more than one molecular test, as this increased the odds of obtaining a successful test.