Friedrichs Nicolaus, Jäger Richard, Paggen Ellen, Rudlowski Christian, Merkelbach-Bruse Sabine, Schorle Hubert, Buettner Reinhard
Institute of Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany.
Mod Pathol. 2005 Mar;18(3):431-8. doi: 10.1038/modpathol.3800292.
Although transcription factors AP-2alpha and AP-2gamma have been implicated in the control of estrogen receptor (ER) and ErbB-2, their impact for breast cancer is still controversial. To better understand the role of AP-2 proteins in mammary neoplasia, the analysis of their spatial expression pattern in normal breast and breast cancer is required. A total of 51 specimens of female breast cancer patients and a tissue microarray containing 93 additional female breast cancer cases were immunohistochemically stained for AP-2alpha, AP-2gamma, ER and ErbB-2. In 70 cases of the tissue microarray, survival data comprising a period of up to 30 years were present. In non-neoplastic breast tissue, AP-2alpha was expressed in the inner glandular cell layer while AP-2gamma was expressed in the outer myoepithelial cell layer. Ductal carcinoma in situ revealed strongly AP-2alpha-positive tumor cells surrounded by a layer of AP-2gamma-positive myoepithelial cells. In invasive carcinoma, expression of AP-2alpha and AP-2gamma was variable. High expression of ER and AP-2alpha showed better survival rates than low expression of these markers. AP-2gamma expression had no effect on survival. These results for the first time reveal a distinct spatial expression pattern of AP-2alpha and AP-2gamma in normal breast and in ductal carcinoma in situ with specific AP-2gamma expression in myoepithelium. High ER and AP-2alpha expression in invasive breast cancer showed favorable survival rates. Therefore, AP-2alpha expression seems to be associated with better prognosis of breast cancer. AP-2gamma expression has no influence on survival reflecting that myoepithelial cells are not involved in the neoplastic process.
尽管转录因子AP - 2α和AP - 2γ已被认为参与雌激素受体(ER)和ErbB - 2的调控,但它们对乳腺癌的影响仍存在争议。为了更好地理解AP - 2蛋白在乳腺肿瘤形成中的作用,需要分析它们在正常乳腺和乳腺癌中的空间表达模式。对51例女性乳腺癌患者的标本以及包含另外93例女性乳腺癌病例的组织芯片进行免疫组织化学染色,检测AP - 2α、AP - 2γ、ER和ErbB - 2。在组织芯片的70例病例中,有长达30年的生存数据。在非肿瘤性乳腺组织中,AP - 2α在内层腺细胞层表达,而AP - 2γ在外层肌上皮细胞层表达。原位导管癌显示AP - 2α强阳性的肿瘤细胞被一层AP - 2γ阳性的肌上皮细胞包围。在浸润性癌中,AP - 2α和AP - 2γ的表达是可变的。ER和AP - 2α高表达者的生存率高于这些标志物低表达者。AP - 2γ的表达对生存无影响。这些结果首次揭示了AP - 2α和AP - 2γ在正常乳腺和原位导管癌中的独特空间表达模式,肌上皮细胞中有特异性的AP - 2γ表达。浸润性乳腺癌中ER和AP - 2α高表达显示出良好的生存率。因此,AP - 2α的表达似乎与乳腺癌较好的预后相关。AP - 2γ的表达对生存无影响,这表明肌上皮细胞不参与肿瘤形成过程。