correlative study of angiogenesis extent and expression of matrix metalloproteinase-9 with upgrading and myometrial invasion in endometrial endometrioid carcinoma

ABSTRACT

Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during tumor changeover and progression. This study was carried out on 60 retrospective endometrial endometrioid carcinoma [EEC] cases in addition to 15 normal endometrial biopsies as controls. EEC cases were grouped according to both histological grade [G], from G1 to G3, and the depth of myometrial [M] invasion, from M1 to M3. The study investigated all cases immunohistochemically to determine their microvessel number and the expression of matrix metalloproteinase-9 [MMP-9] and showed significantly high counts in EEC as a whole over the control endometria [P < 0.001]. Moreover counts of the G1 group overlapped those of the control endometra, increased significantly [P < 0.01] in the G2 and even more in the G3 group. G3 cases, in particular, displayed most microvessels widely scattered in the tumor tissue, in close association with tumor cells and as winding and arborized tubes, often dilated in microaneurysmatic segments. The counts also increased in M2 and M3 [P < 0.001] while those of the M1 group overlapped the counts of control endometria. Expression of MMP-9, evaluated as percentages of positive cases, revealed that the overall EEC cases gave a significant increase [P < 0.01] over the normal control endometria. Also, the frequencies of expression were significantly increased with the histologic grade [P = 0.01] and with the depth of myometrial invasion [P = 0.08]. The increases for MMP-9 were more evident on transition from G2 to G3 than from G1 to G2. The relationship to the depth of invasion revealed that the increases for MMP-9 were found at each depth, mostly on transition from M2 to M3. By contrast, only two of the control biopsies [13.5%] expressed few MMP-9. In EEC, MMP-9, as well, was, expressed by the host stromal cells. These data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with EEC upgrading and advancing depth of invasion. Also, they suggest that EEC cells and some host stromal cell populations cooperate in the tumor progression