Celis Julio E, Gromova Irina, Gromov Pavel, Moreira José M A, Cabezón Teresa, Friis Esbern, Rank Fritz
Danish Centre for Translational Breast Cancer Research (DCTB), Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
FEBS Lett. 2006 May 22;580(12):2935-44. doi: 10.1016/j.febslet.2006.03.080. Epub 2006 Apr 12.
Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and pure apocrine carcinomas. Moreover, specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine cancer.
乳腺癌是一种异质性疾病，涵盖多种组织病理学类型，包括：浸润性导管癌、小叶癌、髓样癌、黏液癌、管状癌和大汗腺癌等。根据丹麦乳腺癌合作组织登记处的数据，纯大汗腺癌约占所有浸润性乳腺癌的0.5%，尽管它们在形态上与其他乳腺病变不同，但目前尚无用于其诊断的标准分子标准。此外，良性大汗腺改变与乳腺癌之间的关系尚不清楚，多年来一直是讨论的话题。最近对乳腺大汗腺大囊肿、正常乳腺组织和乳腺肿瘤的蛋白质组表达谱研究已经确定了在早期和晚期大汗腺病变中存在的特定大汗腺生物标志物[15-羟基前列腺素脱氢酶（15-PGDH）和羟甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）]。这些生物标志物与在纯大汗腺癌中特征性上调的蛋白质（银屑素、S100A9和p53）相结合，提供了一种区分良性大汗腺化生和大汗腺囊性病变的蛋白质表达特征。这些研究还通过前列腺素降解酶15-PGDH的表达，为早期大汗腺病变与纯大汗腺癌之间的直接联系提供了令人信服的证据。此外，针对表达特征成分的特异性抗体已经在大汗腺癌的线性组织学进展中鉴定出前驱病变。最后，对乳腺大汗腺分化早期阶段特征性蛋白质的鉴定，如15-PGDH、HMG-CoA还原酶和环氧化酶2（COX-2），不仅为治疗干预，也为化学预防干预打开了一扇机会之窗。在此，我们结合目前乳腺大汗腺癌的研究现状，综述已发表的和最新的研究结果。
