title: Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta.
abstract: OBJECTIVE
  Our purpose was to investigate the expression of matrix metalloproteinases (MMPs) in gestational trophoblastic diseases and normal first-trimester placenta.
  
  
  METHODS
  Paraffin sections of 16 partial moles, 25 complete moles, 10 gestational choriocarcinomas, and 11 normal first-trimester placentas were studied immunohistochemically for expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1).
  
  
  RESULTS
  Nine (90.0%) of the choriocarcinoma cases showed strong intensity of staining for MMP-1. Choriocarcinoma exhibited significantly stronger staining for MMP-1 than syncytiotrophoblast in normal placenta (P < 0.01), partial mole (P < 0.01), and complete mole (P < 0.01). Choriocarcinoma also showed significantly stronger staining for MMP-1 than the extravillous trophoblast in placenta (P < 0.05). MMP-2 was expressed only in syncytio- and extravillous trophoblasts in normal placenta, partial mole, and complete mole. Choriocarcinoma and the extravillous trophoblast in partial mole and complete mole had significantly stronger staining for MMP-2 than the extravillous trophoblast in placenta (P < 0.05, P < 0.01, P < 0.01, respectively). Choriocarcinoma also exhibited significantly stronger staining for MMP-2 than syncytiotrophoblasts in placenta (P < 0.01), partial mole (P = 0.05), and complete mole (P < 0.01). The expression of MMP-3, MMP-9, and MMP-13 was similar in all four tissues with the predominance of syncytiotrophoblast for MMP-3 and MMP-13 and cytotrophoblast for MMP-9. While 8 (73.0%) placentas, 14 (87.5%) partial moles, and 19 (76.0%) complete moles showed strong immunoreactivity for TIMP-1 in syncytiotrophoblasts, no strong staining was found in choriocarcinomas (P < 0.01, P < 0.01, P < 0.01, respectively).
  
  
  CONCLUSIONS
  The extravillous trophoblast of first-trimester placenta has significantly less expression of MMP-1 than choriocarcinoma and significantly less expression of MMP-2 than choriocarcinoma and extravillous trophoblast of partial and complete mole. The expression of TIMP-1 was significantly less in choriocarcinoma than the syncytiotrophoblast of normal placenta, partial mole, and complete mole. MMPs and their inhibitors may play a role in the pathogenesis of gestational trophoblastic diseases.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Haynal Imre University of Health Sciences, Budapest, Hungary.
authors.forename: G L
authors.initials: GL
authors.lastname: Vegh
authors.forename: Z
authors.initials: Z
authors.lastname: Selcuk Tuncer
authors.forename: V
authors.initials: V
authors.lastname: Fulop
authors.forename: D R
authors.initials: DR
authors.lastname: Genest
authors.forename: S C
authors.initials: SC
authors.lastname: Mok
authors.forename: R S
authors.initials: RS
authors.lastname: Berkowitz
mesh_terms: D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000096:biosynthesis*; D010920:Placenta / Q000737:chemistry / Q000201:enzymology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis*; D014328:Trophoblastic Neoplasms / Q000737:chemistry / Q000201:enzymology*; D014594:Uterine Neoplasms / Q000737:chemistry / Q000201:enzymology*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases