Wolman S R, Sanford J, Ratner S, Dawson P J
Oncor, Inc., Gaithersburg, Maryland, USA.
Mod Pathol. 1995 Apr;8(3):239-43.
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.
男性乳腺癌的发病率较低，这可能反映了与女性乳腺癌不同的病因学因素以及激素依赖性的降低。我们试图通过荧光原位杂交检测22例男性肿瘤和11例男性乳房发育症的X和Y染色体拷贝数，以确定可能反映发病机制改变的男性肿瘤中的基因差异。通过对石蜡块中解离细胞进行流式细胞术，获得了15例浸润性导管癌、4例乳头状肿瘤（3例浸润性和1例导管内乳头状瘤）、2例导管原位癌、1例乳头状瘤以及11例男性乳房发育症的倍体值。对恶性乳头状病变和14例导管肿瘤进行了荧光原位杂交检测。使用抗生物素蛋白-生物素、地高辛配基-抗地高辛配基和直接标记技术相结合的方法，将X和Y染色体着丝粒区域的DNA探针与福尔马林固定石蜡包埋切片反应。通过流式细胞术，7例多模态肿瘤（包括1例原位癌）明显为非整倍体；其余14例恶性肿瘤、乳头状瘤以及11例男性乳房发育症均在二倍体范围内。在2例病例中，由于X和Y染色体的额外拷贝，未被流式细胞术识别的肿瘤中的非整倍体-四倍体克隆被检测为亚群。2例通过荧光原位杂交显示非整倍体亚群的病例，有X染色体拷贝数增加的证据，提示该染色体在肿瘤内优先增加，并且荧光原位杂交结果也支持排除先天性克兰费尔特综合征，尽管不能排除嵌合体。
