Fluorescence in situ hybridization as a tool for microstaging in malignant melanoma

Up to 30-50% of melanomas arise in association with a nevus. Accurately defining, the nevus from the melanoma can significantly affect microstaging. Recently, we showed that a targeted fluorescence in situ hybridization (FISH) assay could distinguish between benign nevi and melanoma with a sensitivity of 87% and specificity of 95%. In this study, we evaluated the potential of this same assay for use in the microstaging of melanoma. We performed FISH on 36 cases of melanoma occurring in association with a nevus and 6 cases of nevoid melanoma with deep dermal involvement. In the melanomas with associated benign nevi, FISH enumeration was performed separately on the histologically malignant and benign components. In the nevoid melanomas, FISH was performed on the deep dermal areas. On the basis of the criteria developed in our earlier studies, we determined the sensitivity of the assay within the malignant areas and the specificity within the benign areas of melanomas with associated nevi. In addition, we evaluated the sensitivity and specificity within a group of six nevoid melanomas with deep dermal involvement. Among melanomas with associated nevi, 28 of 36 cases (78%) tested positively in the histologically malignant areas. The benign nevus components were uniformly negative for all criteria. Six of six nevoid melanomas (100%) tested positively in the deep dermal area. FISH analysis with probes targeting 6p25, 6q23, 11q13 and CEP6 can effectively discriminate the malignant and benign components of melanomas with associated nevi and can be used as an adjunctive tool for microstaging. The assay has high sensitivity for the malignant areas of nevus-associated melanomas and outstanding specificity for the benign areas. The sensitivity is independent of the morphological features, and the assay performs well in nevoid melanoma cases.