Concordance Analysis of the 23-Gene Expression Signature (myPath Melanoma) With Fluorescence In Situ Hybridization Assay and Single Nucleotide Polymorphism Array in the Analysis of Challenging Melanocytic Lesions: Results From an Academic Medical Center

Abstract

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.

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

“…The indeterminate rate was 16%, similar to other ancillary tests for melanoma. 13,16,43,55 Although this study utilized unambiguous nevi and melanomas, future studies will examine histopathologically ambiguous lesions.…”

“…Assays based on comparative genomic hybridization (CGH), gene expression profiles, and fluorescence in situ hybridization (FISH) are among the recently developed laboratory tests for this specific purpose. [13][14][15][16][17] Matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) is a technology ideal for providing proteomics information supporting the pathologist's diagnosis. In a MALDI IMS experiment, thin tissue sections are prepared similarly to traditional histopathological experiments and analyzed using a MALDI mass spectrometer.…”

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…Noninvasive molecular tests have been developed to provide additional information for pathologists in their assessment of a primary cutaneous melanocytic lesion for which malignant potential is uncertain. One of the tests assesses the expression of 23 genes to determine whether the lesion is benign or malignant; the genes, which are involved in cell differentiation, cell-cell signaling, and immune response, vary in a predictable manner between nevi and malignant melanoma (Table 1) [50][51][52][53][54][55][56][57][58].…”

“…RNA is extracted from the processed biopsy specimen, and the expression of the 23 genes is determined by qRT-PCR. A numeric score (ranging from -16.7 to 11.7) is determined; the results are reported as benign (with a numeric range from -16.7 to -2.1), intermediate (with a numeric range from -2.0 to -0.1), or malignant (with a numeric range from 0 to 11.1) [50][51][52][53][54][55][56][57][58].…”

“…However, depending on the study, the test resulted in an indeterminate (intermediate) diagnosis for 2.9 to 16.2% of the lesions. Subsequently, a 35-GEP test was developed to improve the classification of the pigmented lesions that were diagnosed as intermediate using the 23-GEP test [50][51][52][53][54][55][56][57][58].…”