Significance of matrix metalloproteinase-7 [correction of matrix metalloproteinase-2], -11 and tissue inhibitor of metalloproteinase-1 expression in normal, hyperplastic and neoplastic endometrium.

ABSTRACT

BACKGROUND: Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) are key factors in the degradation of extracellular matrix and basement membranes. This study aimed to examine the expressions of MMP-7 and -11 and TIMP-1 in normal, hyperplastic and neoplastic endometrium and their correlation to clinicopathologic factors. PATIENTS AND METHODS: Tissue samples of 40 normal endometria, 20 endometrial hyperplasias and 120 endometrial endometrioid adenocarcinomas were used for the study. Immunohistochemical staining for MMP-7 and -11 and TIMP-1 protein was performed on formalin-fixed and paraffin-embedded tissue samples. These expressions were represented as incidence of expression. RESULTS: MMP-7 was highly expressed in the glands of the basal and functional layers during the proliferative and menstrual phases. MMP-11 expression in the gland of the basal layer and the stroma of the functional layer fluctuated during the menstrual cycle. TIMP-1 was highly expressed in the late secretory and menstrual phases. MMP-7 was expressed at significantly higher levels in endometrial hyperplasia than normal endometrium, whereas MMP-11 was expressed at lower levels. In endometrial adenocarcinoma, MMP-7, MMP-11 and TIMP-1 were expressed at the same levels as in hyperplasia. MMP-7 expression in endometrial carcinoma was correlated with myometrial invasion and estrogen receptor expression. The expression of MMP-7 in the adjacent stroma was associated with a poor prognosis. CONCLUSION: MMP-7, MMP-11 and TIMP-1 expression may be regulated by the menstrual cycle, and related to the degradation and remodeling of the normal endometrium. MMP-7 expression might be a prognostic factor in endometrial carcinoma.