Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer.
OBJECTIVE
Matrix metalloproteinases (MMPs) and their physiological inhibitors, the tissue inhibitors of MMPs (TIMPs), play a key role in tumor cell invasion, angiogenesis, and growth. The aim of this study was to determine the expression and cellular distribution of MMP-26, TIMP-3, and TIMP-4 in endometrial cancers and benign endometrium throughout the menstrual cycle and the correlation with tumor histological subtype, stage, and grade.


METHODS
Immunohistochemical analysis using polyclonal antibodies generated against pro- and active MMP-26, and mono- and polyclonal antibodies specific to TIMP-3 and TIMP-4, respectively, was performed.


RESULTS
MMP-26, TIMP-3, and TIMP-4 are expressed in endometrial carcinomas (N = 86) and benign endometrium (N = 50) from various stages of the menstrual cycle. Semi-quantitative analysis of staining intensity indicated that endometrial carcinomas expressed more MMP-26, TIMP-3, and TIMP-4 compared to benign endometrium from the postmenopausal period, but not from the secretory phase of the menstrual cycle. The highest staining intensity was associated with endometrial epithelial cells, followed by vascular endothelial cells, myometrial smooth muscle cells, and endometrial stromal cells. Increased staining intensity of MMP-26 and TIMP-3 correlated with grade III tumors and MMP-26 and TIMP-4 with the depth of myometrial invasion in tumors histologically characterized as endometrioid adenocarcinoma, clear-cell, and papillary serous carcinoma staged/graded based on FIGO criteria.


CONCLUSIONS
MMP-26 and TIMP-4 are expressed in endometrium and endometrial carcinoma and their elevated expression and correlation with myometrial invasion suggests that MMP-26 and TIMP-4 may play a key role in endometrial tumor progression.
Tunuguntla
Renuka
R
Department of Obstetrics/Gynecology, University of Florida, Gainesville, FL 32610, USA.
Ripley
Daylene
D
Sang
Qing Xiang Amy
QX
Chegini
Nasser
N
D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018283:Cystadenocarcinoma, Papillary / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000201:enzymology / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D053505:Matrix Metalloproteinases, Secreted; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C410599:MMP26 protein, human