Expression of TGF-ß signaling proteins in normal placenta and gestational trophoblastic disease
Y.H. Xuan1,6, Y.-L. Choi3, Y.K. Shin2, G.-H. Ahn3, K.H. Kim4, W.J. Kim5, H.-C. Lee7 and S.-H. Kim1
1Department of Pathology, 5Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Korea, 2Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University, College of Pharmacy, Seoul, Korea, 3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 4Department of Pathology and Molecular Medicine, Eulji University School of Medicine, Daejeon, Korea, 6Department of Pathology, Yanbian University College of Medicine, Yanji, China and 7Department of Pathology, Seoul National University, College of medicine, Seoul, Korea
Offprint requests to: Seok-Hyung Kim, M.D., Ph.D., Department of Pathology, College of Medicine, Chungbuk National University, 62 Kaesin-dong, Cheongju, Chungbuk, 361-763, South Korea. e-mail: email@example.com.
Summary. The transforming growth factor ß (TGF-ß) is a vital regulator of placental development and functions. TGF-ß 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-ß 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 ß1/2, TGF-ß receptor type I (TßRI), TßRII, Smad 2/3, and Smad 4 antibodies on paraffin blocks. In the case of normal placenta, maximal levels of all TGF-ß signaling molecules were observed in villous trophoblast in the first trimester, which decreased with gestational age. Expression of all the TGF-ß signaling proteins except Smad2/3, was significantly enhanced in various moles, relative to normal trophoblast. Moreover, TGF-ß signaling molecules were significantly downregulated in choriocarcinoma, compared to moles. In particular, TßRI and Smad2/3 levels were lower in choriocarcinoma than normal villous trophoblast (TßRI: p<0.025, Smad2/3: p<0.001). In conclusion, the TGF-ß 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. Histol Histopathol 22, 227-234 (2007)
Key words: TGFB, Immunohistochemistry, Hydatidiform mole, Choriocarcinoma