PMID- 12798711 OWN - NLM STAT- MEDLINE DCOM- 20030627 LR - 20231213 IS - 0090-8258 (Print) IS - 0090-8258 (Linking) VI - 89 IP - 3 DP - 2003 Jun TI - Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer. PG - 453-9 AB - 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. CONCLUSION: 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. FAU - Tunuguntla, Renuka AU - Tunuguntla R AD - Department of Obstetrics/Gynecology, University of Florida, Gainesville, FL 32610, USA. FAU - Ripley, Daylene AU - Ripley D FAU - Sang, Qing Xiang Amy AU - Sang QX FAU - Chegini, Nasser AU - Chegini N LA - eng GR - CA78646/CA/NCI NIH HHS/United States GR - HD37432/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Tissue Inhibitor of Metalloproteinase-3) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - EC 3.4.24.- (MMP26 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.- (Matrix Metalloproteinases, Secreted) SB - IM MH - Adenocarcinoma, Clear Cell/enzymology/metabolism/pathology MH - Carcinoma, Endometrioid/enzymology/metabolism/pathology MH - Cystadenocarcinoma, Papillary/enzymology/metabolism/pathology MH - Endometrial Neoplasms/enzymology/*metabolism/pathology MH - Endometrium/enzymology/metabolism MH - Epithelial Cells/enzymology/metabolism/pathology MH - Female MH - Humans MH - Immunohistochemistry MH - Matrix Metalloproteinases/*biosynthesis MH - Matrix Metalloproteinases, Secreted MH - Tissue Inhibitor of Metalloproteinase-3/*biosynthesis MH - Tissue Inhibitor of Metalloproteinases/*biosynthesis MH - Tissue Inhibitor of Metalloproteinase-4 EDAT- 2003/06/12 05:00 MHDA- 2003/06/28 05:00 CRDT- 2003/06/12 05:00 PHST- 2003/06/12 05:00 [pubmed] PHST- 2003/06/28 05:00 [medline] PHST- 2003/06/12 05:00 [entrez] AID - S0090825803000775 [pii] AID - 10.1016/s0090-8258(03)00077-5 [doi] PST - ppublish SO - Gynecol Oncol. 2003 Jun;89(3):453-9. doi: 10.1016/s0090-8258(03)00077-5.