Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta

Gyorgy L. Vegh, Z. Selcuk Tuncer, V. Fülöp, David R. Genest, Samuel C. Mok, Ross S. Berkowitz

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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). Conclusion. 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.

Original languageEnglish
Pages (from-to)248-253
Number of pages6
JournalGynecologic Oncology
Volume75
Issue number2
DOIs
Publication statusPublished - Nov 1999

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Gestational Trophoblastic Disease
Matrix Metalloproteinase Inhibitors
Trophoblasts
Choriocarcinoma
Placenta
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 13
Staining and Labeling
Matrix Metalloproteinase 3
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 9
First Pregnancy Trimester
Matrix Metalloproteinases
Paraffin

Keywords

  • MMP
  • Placenta
  • TIMP
  • Trophoblastic disease

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta. / Vegh, Gyorgy L.; Selcuk Tuncer, Z.; Fülöp, V.; Genest, David R.; Mok, Samuel C.; Berkowitz, Ross S.

In: Gynecologic Oncology, Vol. 75, No. 2, 11.1999, p. 248-253.

Research output: Contribution to journalArticle

Vegh, Gyorgy L. ; Selcuk Tuncer, Z. ; Fülöp, V. ; Genest, David R. ; Mok, Samuel C. ; Berkowitz, Ross S. / Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta. In: Gynecologic Oncology. 1999 ; Vol. 75, No. 2. pp. 248-253.
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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). Conclusion. 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.",
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AU - Vegh, Gyorgy L.

AU - Selcuk Tuncer, Z.

AU - Fülöp, V.

AU - Genest, David R.

AU - Mok, Samuel C.

AU - Berkowitz, Ross S.

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N2 - 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). Conclusion. 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.

AB - 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). Conclusion. 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.

KW - MMP

KW - Placenta

KW - TIMP

KW - Trophoblastic disease

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