Breast cancer in males: DNA content and sex chromosome constitution.

1995 
: The infrequent occurrence of breast cancer in males may reflect different etiologic factors and decreased hormonal dependence in comparison with the disease in females. We have attempted to define genetic differences in tumors of males that might reflect alterations in pathogenesis, by examining 22 tumors and 11 examples of gynecomastia for ploidy in relation to X- and Y- chromosome copy number by fluorescence in situ hybridization. Ploidy values were obtained for 15 infiltrating ductal and four papillary tumors (three invasive and one intraductal), two ductal carcinomas in situ, one papilloma, and 11 cases of gynecomastia by flow cytometry of disaggregated cells from the paraffin blocks. The malignant papillary lesions and 14 of the ductal tumors were examined by fluorescence in situ hybridization. DNA probes for pericentromeric regions of the X and Y chromosomes were reacted with formalin-fixed paraffin-embedded sections using a combination of avidin-biotin, digoxigenin-antidigoxigenin, and direct-labeling techniques. Seven multimodal tumors, including one carcinoma in situ, were clearly aneuploid by flow cytometry; the remaining 14 malignant tumors, the papilloma, and 11 examples of gynecomastia were within the diploid range. In two cases, aneuploid-tetraploid clones in tumors that were not recognized by flow cytometry were detected as subpopulations because of extra copies of the X and Y chromosomes. Two cases with aneuploid subpopulations by fluorescence in situ hybridization showed evidence of excess X-chromosome copy number, suggestive of preferential increase of this chromosome within the tumor, and the fluorescence in situ hybridization results also supported exclusion of constitutional Klinefelter's syndrome, although mosaicism could not be excluded.
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