Lee Yonghee, Kim Kyu-Rae, McKeon Frank, Yang Annie, Boyd Theonia K, Crum Christopher P, Parast Mana M
Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Pathology, College of Medicine, Pochon CHA University, Bundang CHA General Hospital, Sungnam City, Kyonggi-do 463-712, South Korea.
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.
Hum Pathol. 2007 Jul;38(7):1003-1013. doi: 10.1016/j.humpath.2006.12.012. Epub 2007 Mar 30.
Several trophoblast phenotypes, including cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast, emerge during gestation. To clarify the lineage relationship between these subtypes, we profiled p63 localization in developing and term placental tissue, as well as in trophoblastic tumors, using antibodies specific to full-length (TAp63) and one against all p63 isoforms (TAp63 and DeltaNp63). Localization of p63 was compared with that of biomarkers of proliferation and trophoblastic differentiation, including mib-1, inhibin, and MelCAM. In early gestation, p63 was localized principally to villous cytotrophoblast after contact with the villous mesenchyme, absent in the trophoblast columns, and early implantation trophoblast. In the maturing placenta, intraplacental perivillous fibrin correlated with the emergence of a p63-positive "transitional" (vacuolated) extravillous trophoblast from cytotrophoblast, which differentiated further into a "mature" p63-negative extravillous trophoblast. The same lineage pathway emerged from entrapped villi on the chorionic membrane. Virtually all p63 immunopositivity was attributed to dominant-negative p63. The immunophenotypic patterns seen in the immature and mature placenta permit the resolution of all trophoblastic phenotypes within 3 lineage pathways of cytotrophoblast differentiation, including cytotrophoblast-to-trophoblast column/implantation site, cytotrophoblast-to-syncytiotrophoblast, and cytotrophoblast-to-mature extravillous trophoblast. In the latter pathway, a transitional (vacuolated) p63-positive extravillous trophoblast emerges from and links cytotrophoblast to mature extravillous trophoblast in intraplacental fibrin, chorionic membrane, and basal plate. The placental trophoblast is thus resolved within this continuum of differentiation. Terms such as transitional and mature extravillous trophoblast are proposed to reflect the differentiation phases of this unique epithelium. p63 staining patterns in trophoblastic tumors reflect timing of neoplastic transformation during trophoblastic differentiation.
在妊娠期间会出现几种滋养层细胞表型，包括细胞滋养层细胞、合体滋养层细胞和绒毛外滋养层细胞。为了阐明这些亚型之间的谱系关系，我们使用针对全长（TAp63）的特异性抗体以及一种针对所有p63亚型（TAp63和DeltaNp63）的抗体，分析了发育中和足月胎盘组织以及滋养层细胞瘤中p63的定位。将p63的定位与增殖和滋养层细胞分化的生物标志物（包括mib-1、抑制素和MelCAM）的定位进行了比较。在妊娠早期，p63主要定位于与绒毛间充质接触后的绒毛细胞滋养层细胞，在滋养层细胞柱和早期植入的滋养层细胞中不存在。在成熟胎盘中，胎盘内绒毛周围纤维蛋白与细胞滋养层细胞中p63阳性的“过渡性”（空泡化）绒毛外滋养层细胞的出现相关，该细胞进一步分化为“成熟”的p63阴性绒毛外滋养层细胞。相同的谱系途径也出现在绒毛膜上被困的绒毛中。几乎所有的p63免疫阳性都归因于显性负性p63。在未成熟和成熟胎盘中看到的免疫表型模式允许在细胞滋养层细胞分化的3个谱系途径内解析所有滋养层细胞表型，包括细胞滋养层细胞到滋养层细胞柱/植入部位、细胞滋养层细胞到合体滋养层细胞以及细胞滋养层细胞到成熟绒毛外滋养层细胞。在后者途径中，一个过渡性（空泡化）的p63阳性绒毛外滋养层细胞在胎盘内纤维蛋白、绒毛膜和基底板中从细胞滋养层细胞中出现并将其与成熟绒毛外滋养层细胞连接起来。因此，胎盘滋养层细胞在这个连续的分化过程中得以解析。提出了诸如过渡性和成熟绒毛外滋养层细胞等术语来反映这种独特上皮细胞的分化阶段。滋养层细胞瘤中的p63染色模式反映了滋养层细胞分化过程中肿瘤转化的时间。
