Mühlhauser J, Crescimanno C, Kaufmann P, Höfler H, Zaccheo D, Castellucci M
Department of Anatomy, RWTH Aachen, Germany.
J Histochem Cytochem. 1993 Feb;41(2):165-73. doi: 10.1177/41.2.8093455.
It is well known that growth factors and proto-oncogenes play a pivotal role in organogenesis as well as in tumor development. The human placenta is a rapidly growing organ which shares some aspects with malignant tumors. We have studied the expression of epidermal growth factor receptor (EGF-R) and the receptor encoded by the c-erbB-2 proto-oncogene in first- and third-trimester human placentas. We compared these expression patterns with that of the proliferation marker Ki-67. By immunohistochemistry, EGF-R was intensively expressed in the villous cytotrophoblast in the first trimester. The apical plasma membrane of the syncytium was weakly stained. In placental villi from the third trimester the reaction product for EGF-R was most intense in single villous cytotrophoblastic cells and along the apical plasma membrane of the syncytium, whereas the basal plasma membrane was much less stained. C-erbB-2 protein product was expressed in the first and third trimesters along the apical membrane of the syncytiotrophoblast. Concerning the extravillous trophoblast in cell islands and cell columns, EGF-R was expressed in the cells proximal to the villous stroma whereas the distal cells were c-erbB-2 positive. The Ki-67 antibody revealed the proliferative character of the villous cytotrophoblast and of the EGF-R-positive extravillous trophoblast. In contrast, most of the c-erbB-2-positive cells were Ki-67 negative. By in situ hybridization, c-erbB-2 transcripts were found in all types of villous and extravillous trophoblast, including those that did not express c-erbB-2 protein product. Our data indicate that EGF-R expression is strongly related to the proliferative trophoblast and, with advancing pregnancy, to the differentiated villous trophoblast.off contrast, expression of c-erB-2 protein product occurs only in more advanced stages of trophoblast differentiation, although transcripts of c-erbB-2 are found in both proliferative and differentiated trophoblast. In addition, the coexpression of EGF-R and c-erbB-2 protein product in the syncytiotrophoblast suggests their involvement in complex regulation of hormones and growth factors.
众所周知，生长因子和原癌基因在器官发生以及肿瘤发展过程中起着关键作用。人类胎盘是一个快速生长的器官，它在某些方面与恶性肿瘤相似。我们研究了表皮生长因子受体（EGF-R）以及由c-erbB-2原癌基因编码的受体在妊娠早期和晚期人类胎盘中的表达情况。我们将这些表达模式与增殖标记物Ki-67的表达模式进行了比较。通过免疫组织化学方法，EGF-R在妊娠早期的绒毛细胞滋养层中强烈表达。合体滋养层的顶端质膜染色较弱。在妊娠晚期的胎盘绒毛中，EGF-R的反应产物在单个绒毛细胞滋养层细胞以及合体滋养层的顶端质膜处最为强烈，而基底质膜染色则少得多。c-erbB-2蛋白产物在妊娠早期和晚期均沿着合体滋养层的顶端膜表达。关于细胞岛和细胞柱中的绒毛外滋养层，EGF-R在靠近绒毛基质的细胞中表达，而远端细胞c-erbB-2呈阳性。Ki-67抗体显示了绒毛细胞滋养层以及EGF-R阳性的绒毛外滋养层的增殖特性。相比之下，大多数c-erbB-2阳性细胞Ki-67呈阴性。通过原位杂交，在所有类型的绒毛和绒毛外滋养层中都发现了c-erbB-2转录本，包括那些不表达c-erbB-2蛋白产物的细胞。我们的数据表明，EGF-R的表达与增殖性滋养层密切相关，并且随着妊娠进展，与分化的绒毛滋养层也密切相关。相比之下，c-erB-2蛋白产物仅在滋养层分化的更晚期阶段表达，尽管在增殖性和分化的滋养层中都发现了c-erbB-2的转录本。此外，EGF-R和c-erbB-2蛋白产物在合体滋养层中的共表达表明它们参与了激素和生长因子的复杂调节。
