Objective: To evaluate the diagnostic sensitivity of fluorescence in situ hybridization (FISH) using probes targeting 6p25, 6q23, 11q13, and Cep6 in melanoma subtypes. Design: Blinded comparison of chromosomal copy number changes detected using FISH targeting 6p25, 6q23, 11q13, and Cep6 in benign nevi and melanoma subtypes. Setting: Dermatopathology Laboratory, Department of Dermatology, Northwestern University, Chicago, Illinois. Participants: One hundred ten individuals with benign nevi and 123 with melanoma (70 superficial spreading, 28 lentigo maligna, 22 nodular, and 3 acral lentiginous melanomas). Main Outcome Measures: Sensitivity of previously developed criteria using FISH using probes targeting 6p25, 6q23, 11q13, and Cep6 in the melanoma subtypes. Results: Overall, sensitivity was 83.0% and specificity was 94.0%. The 6p25 gain criterion had the highest sensitivity overall and in each subtype. The assay was most sensitive in the subgroups of nodular and acral melanomas and least sensitive in the superficial spreading subtype. The 11q13 gain was more commonly seen in chronically sun-damaged skin and infrequently in non-chronically sun-damaged skin. Conclusions: Heterogeneous changes in melanoma occur at the molecular level, and the changes are different among melanoma subtypes. Clonal abnormalities in chromosome 6 with increased copies of the short arm relative to the long arm are common in all melanoma subtypes, suggesting that isochromosome 6 is common in all variants of cutaneous melanoma subtypes. An increase in copy number of 11q13 is most frequent in chronically sun-damaged melanomas.
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