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


  • Department of Biomedical Sciences and Human Oncology (R. Ria, A. Vacca, A. M. Roccaro), Department of Obstetrics and Gynaecology (G. Loverro, G. Cormio, L. Selvaggi), Department of Human Anatomy and Histology (D. Ribati), University of Bari Medical School, I-70124, Bari, Italy

A. Vacca, Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, Policlinico, Piazza Giulio Cesare 11, I-70124 Bari, Italy. Tel.: + 39 80 559 31 06; fax: + 39 80 547 88 20; e-mail:


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.