Angiogenesis extent and expression of matrix metalloproteinase‐2 and ‐9 agree with progression of ovarian endometriomas

Roberto Ria, R Ria, Giuseppe Loverro, G Loverro, A Vacca, Angelo Vacca, Doménico Ribatti, D Ribatti, Gennaro Cormio, G Cormio, Aldo M. Roccaro, A M Roccaro, L Selvaggi, Luigi Selvaggi
European journal of clinical investigation · 2002 · vol. 32(3) , pp. 199–206 · doi:10.1046/j.1365-2362.2002.00960.x · PMID:11895472 · W1975706974
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Ovarian endometriomas show increased angiogenesis and matrix metalloproteinase-2 and -9 mRNA expression, particularly in stage IV disease, correlating with disease progression.

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Abstract

BACKGROUND: Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated in tumour changeover and progression. METHODS: Tissues from 44 biopsies of stage III and IV ovarian endometriomas, and 10 biopsies of normal (control) endometrium were investigated immunohistochemically to count microvessels, and by in situ hybridization to assess the expression of mRNA of matrix metalloproteinase-2 (MMP-2) and MMP-9. Implants of the tissues were investigated in the chick embryo chorioallantoic membrane (CAM) assay to determine their angiogenic capacity. RESULTS: The endometriomas displayed significantly higher counts than normal endometria and the highest values were associated with the deepest invasion level (stage IV). Microvessels localized in close association with ectopic endometrial cells in the form of winding and arborized tubes, often dilated in microaneurysmatic segments. These were absent in normal endometrium. Expression of MMP-2 and MMP-9 mRNA, evaluated as percentages of positive biopsies and intensity of expression, was up-regulated in endometriomas and more pronounced in stage IV. MMP-2 and MMP-9 mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblasts and macrophages, whereas the control endometrium showed very little expression of MMP-2 mRNA in a few endothelial cells and no expression of MMP-9 mRNA. Implants from stage IV endometrioma induced a more intense vasoproliferative response than those from stage III, while no vasoproliferative response was induced by the normal endometrium. CONCLUSION: These data suggest that angiogenesis and degradation of extracellular matrix occur together in endometriosis and are more pronounced in stage IV, and that endometriosis cells and some host stromal cell populations co-operate in disease progression.

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Condition tags

mesh:D004715endometriosisendometrioma

MeSH descriptors

Endometriosis Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Neovascularization, Pathologic Ovarian Cysts Adult Aged Aged, 80 and over Allantois Animals Chick Embryo Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans

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References (47)

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