Fluorescence in situ hybridization as a diagnostic modality in melanocytic neoplasms

It has well been established by comparative genomic hybridizations that melanocytic neoplasms have chromosomal copy number aberrations not seen in benign melanocytic nevi. In a rigorous study involving over 400 melanocytic neoplasms we recently evaluated the potential of a number of chromosomal loci frequently altered in melanoma but not in nevi as potential targets for a fluorescence in situ based assay. After evaluating 14 potential chromosomal loci arranged in various 4 probe panels, 6p25, 6q23, Cep6 and 11q13 were identified as the combination of targets best able to differentiate between malignant melanoma and benign nevi. Melanocytic neoplasms were considered as positive for melanoma if any of the following criteria were met; greater than 29% of enumerated cells showed gains in 6p25; greater than 38% of cells showed gains in 11q13; greater than 55% of cells show more copies of 6p25 than Cep6; or if greater than 42% of cells have less copies of 6q23 than Cep6. In a validation set, this 4 probe assay targeting these loci was able to differentiate between melanoma and nevi with a sensitivity of 86.7% and specificity of 95.4%. In this paper we review the multiple steps involved in development of this assay as well as the subsequent performance of this assay in a number of studies looking at its utility in specific differential diagnoses in melanocytic pathology.