Angiogenesis extent and expression of matrix metalloproteinase-2 and-9 correlate with upgrading and myometrial invasion in endometrial carcinoma

Background: Changes in angiogenesis and expression of extracellular matrix- degrading enzymes have been substantiated during tumour changeover and prog ression. Methods: Tissues from 64 biopsies of endometrial carcinoma (EC) and 15 biop sies of normal (control) endometrium were investigated immunohistochemicall y to determine their microvessel number, and by in situ hybridisation to de termine the expression of mRNA of the matrix metalloproteinase-2 (MMP-2, ge latinase A) and metalloproteinase-9 (MMP-9 gelatinase B). EC were grouped a ccording to both histological grade (G) G1 to G3 and depth of myometrial (M ) invasion M1 to M3. Results: EC as a whole gave significantly higher counts over control endome tria. Counts of the GI group overlapped those of the control group, increas ed significantly in the G2 and even more in the G3 group. G3 biopsies in pa rticular also displayed most microvessels widely scattered in the tumour ti ssue, in close association with tumour cells, and as winding and arborized tubes, often dilated in microaneurysmatic segments. Counts also increased i n M2 and M3. Expression of the MMP-2 and MMP-9mRNA, evaluated as percentage s of positive biopsies and intensity of expression, were upregulated with t he transition from control and G1 groups to G2 and G3, and in relation to a dvancing depth of invasion. In EC, MMP-2 and MMP-9mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblas ts and macrophages. In the control biopsies, poor expression of MMP-2mRNA i n few endothelial cells and no expression of MMP-9mRNA were detected. Conclusion: These in situ data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with EC upgrading and advancing depth of invasion, and that EC cells and some host stromal cell populations cooperate in tumour progression.