Trisomy 6 in basal cell carcinomas correlates with metastatic potential: a dual color fluorescence in situ hybridization study on paraffin sections.

BACKGROUND Most basal cell carcinomas (BCCs) are indolent lesions; a few become locally aggressive or even metastatic. Little is known about the molecular and genetic alterations in this malignant transformation. Conventional karyotyping in BCC has revealed a high frequency of nonclonal, structural rearrangements, with few cases that show multiple, unrelated, small clones suggestive of a multicellular origin. Trisomy 6 was described recently in a few BCCs, but the biologic significance of the appearance of trisomy 6 in BBCs was not clear. METHODS Thirty cases including 4 metastatic, 4 locally aggressive, and 22 conventional nonaggressive BCCs were studied. Fluorescence in situ hybridization (FISH) was performed on 4 microm tissue sections, using alpha-centromeric enumeration probes for chromosome 6 (SpectrumGreen, Vysis Inc., Downers Grove, IL) and chromosome 4 (SpectrumOrange, Vysis Inc., Downers Grove, IL, used as disomic cell control). Trisomy 6 was semiquantitated within tumor cells and nonneoplastic cells in each case. RESULTS Trisomy 6 was identified in all 4 metastatic BCCs within tumor cells and in corresponding BCCs at the primary cutaneous site in 2 of these 4 cases. Two locally aggressive BCCs, 1 of which had preceding radiation exposure, also showed trisomy 6. All nonaggressive BCCs and nonneoplastic cells were disomic for chromosome 6. CONCLUSIONS Trisomy 6 has been identified as a cytogenetic aberration representative of tumor cells in aggressive and metastatic BCC. None of the nonaggressive BCCs in this study demonstrated trisomy 6. Acquisition of trisomy 6 by tumor cells in BCC may lead to the emergence of metastatic potential. Additional studies to define the underlying mechanisms may be valuable in preventing aggressive behavior in BCC.