Xuan Y H, Choi Y L, Shin Y K, Ahn G H, Kim K H, Kim W J, Lee H C, Kim S H
Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Korea.
Histol Histopathol. 2007 Mar;22(3):227-34. doi: 10.14670/HH-22.227.
The transforming growth factor beta (TGF-beta) is a vital regulator of placental development and functions. TGF-beta exerts several modulatory effects on trophoblast cells, such as inhibition of proliferation and invasiveness, and stimulation of differentiation by inducing multinucleated cell formation. In this study, we determine the expression patterns of TGF-beta signaling molecules in normal trophoblast, various hydatidiform mole types and choriocarcinoma. A total of 132 cases, including 51 normal placenta (20 first trimester, 11 second trimester, and 20 third trimester) and 81 gestational trophoblastic diseases (17 choriocarcinoma, and 64 hydatidiform moles: 39 complete, 6 partial, and 19 invasive) were immunohistochemically analyzed with anti-TGF beta1/2, TGF-beta receptor type I (TbetaRI), TbetaRII, Smad 2/3, and Smad 4 antibodies on paraffin blocks. In the case of normal placenta, maximal levels of all TGF-beta signaling molecules were observed in villous trophoblast in the first trimester, which decreased with gestational age. Expression of all the TGF-beta signaling proteins except Smad2/3, was significantly enhanced in various moles, relative to normal trophoblast. Moreover, TGF-beta signaling molecules were significantly downregulated in choriocarcinoma, compared to moles. In particular, TbetaRI and Smad2/3 levels were lower in choriocarcinoma than normal villous trophoblast (TbetaRI: p<0.025, Smad2/3: p<0.001). In conclusion, the TGF-beta signaling pathway plays an important role in the pathogenesis and progression of gestational trophoblastic disease, and may thus be employed as a potential therapeutic target and a diagnostic biomarker.
转化生长因子β（TGF-β）是胎盘发育和功能的重要调节因子。TGF-β对滋养层细胞发挥多种调节作用，如抑制增殖和侵袭，并通过诱导多核细胞形成来刺激分化。在本研究中，我们确定了TGF-β信号分子在正常滋养层、各种葡萄胎类型和绒毛膜癌中的表达模式。总共132例病例，包括51例正常胎盘（20例孕早期、11例孕中期和20例孕晚期）和81例妊娠滋养细胞疾病（17例绒毛膜癌和64例葡萄胎：39例完全性、6例部分性和19例侵袭性），在石蜡块上用抗TGFβ1/2、I型TGF-β受体（TβRI）、TβRII、Smad 2/3和Smad 4抗体进行免疫组织化学分析。在正常胎盘的情况下，所有TGF-β信号分子的最高水平在孕早期的绒毛滋养层中观察到，其随孕周增加而降低。相对于正常滋养层，除Smad2/3外的所有TGF-β信号蛋白在各种葡萄胎中的表达均显著增强。此外，与葡萄胎相比，绒毛膜癌中TGF-β信号分子显著下调。特别是，绒毛膜癌中的TβRI和Smad2/3水平低于正常绒毛滋养层（TβRI：p<0.025，Smad2/3：p<0.001）。总之，TGF-β信号通路在妊娠滋养细胞疾病的发病机制和进展中起重要作用，因此可能被用作潜在的治疗靶点和诊断生物标志物。
