Objective: To study the expression of matrix metalloproteinase (MMP)-2, 9 and tissue inhibitor of metalloproteinase (TIMP)-1, 2 protein in human endometrial carcinoma tissue and its relation to the invasion and metastasis of endometrial carcinoma.
Methods: Immunocytochemistry and zymography techniques were used to measure the MMP-2, MMP-9, TIMP-1, TIMP-2 protein levels and activities in endometrial carcinoma tissue of 37 patients and control group composed of 7 normal postmenstrual endometrial samples.
Results: The MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins mainly expressed in endometrial carcinoma cells, glandular cells and endothelial cells. The strongly positive expression proportions of MMP-2, 9 and TIMP-1 proteins in grade III carcinoma cells were respectively 73%, 20% and 67%, which were higher than those in grade II (13%, 0, 27%) and grade I (0) ones (P < 0.05). They were also higher in endometrial carcinoma with deep layer invasion ones (63%, 16%, 68%) and lymph node metastasis ones (4/4, 3/4, 4/4). TIMP-2 did not show different expression with the tumor invasion and metastasis. In endothelial cells of grade III carcinoma tissue the strongly positive expression proportions of MMP-2 (60%) and TIMP-1 (60%) proteins, not MMP-9, were found in higher amount comparing with those in grade II (20%) and grade I (1/7) tumor tissues (P < 0.05). The density of above four proteins were all found very low in the normal postmenopausal endometrial tissues (P < 0.05). By zymography test the active MMP-2 was the main protein form in adenocarcinoma tissue.
Conclusions: MMP-2 and MMP-9 expression levels in adenocarcinoma tissue correlate with the histologic grade and invasion/metastasis trend. Active MMP-2 is the main form in endometrial cancer.