Department of Biomedical and Neuromotor Sciences, University of Bologna, Unit of Anatomic Pathology "M. Malpighi", Bellaria Hospital, Via Altura, 3, 40139, Bologna, Italy.
Institute of Pathology and Molecular Pathology, University Hospital Zürich, Zürich, Switzerland.
Virchows Arch. 2018 Aug;473(2):155-163. doi: 10.1007/s00428-018-2377-2. Epub 2018 May 25.
X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.
X 染色体获得先前已在男性乳腺癌（MBC）中描述过。雄激素受体（AR）基因位于 X 染色体上。本研究旨在探讨 X 染色体获得在 MBC 发展中的作用及其与 AR 基因拷贝数和表达的关系。通过荧光原位杂交（FISH）评估了 66 例男性浸润性和原位导管乳腺癌、34 例与癌症相关的男性乳腺发育症和 11 例无肿瘤男性乳腺发育症的 X 染色体状态。检测了 AR 扩增情况。通过免疫组织化学（IHC）研究了 AR 表达。此外，还评估了 AR 甲基化状态。X 染色体获得在 74.7%的浸润性导管癌、20.6%的原位导管癌和 20.6%的与癌症相关的男性乳腺发育症中观察到，而所有无肿瘤的男性乳腺发育症均显示野生 X 染色体状态。当 AR 基因拷贝数增加时，与 X 染色体的数量平行增加。在测试的所有 MBC 中均观察到 AR IHC 表达。AR 基因甲基化状态显示低水平或不存在甲基化。这些数据表明 X 染色体可能在男性乳腺上皮的肿瘤转化中发挥作用。X 染色体获得与 AR 基因多倍体平行。多倍体 AR 基因显示低甲基化水平和高 AR 蛋白表达在 IHC 上。在制定 MBC 治疗计划时应考虑这些数据。
