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


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.


CONCLUSIONS
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.
Obokata
Akane
A
Department of Clinical Cytology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan.
Watanabe
Jun
J
Nishimura
Yukari
Y
Arai
Tsutomu
T
Kawaguchi
Miwa
M
Kuramoto
Hiroyuki
H
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D004714:Endometrial Hyperplasia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053507:Matrix Metalloproteinase 11 / Q000096:biosynthesis*; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D009367:Neoplasm Staging; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*
D019715:Tissue Inhibitor of Metalloproteinase-1; D053507:Matrix Metalloproteinase 11; D020783:Matrix Metalloproteinase 7