Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer.
Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer.
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DOI：
10.1016/s0090-8258(03)00077-5
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发表时间：
2003-06
影响因子：
4.7
通讯作者：
R. Tunuguntla;D. Ripley;Q. Sang;N. Chegini
中科院分区：
文献类型：
--
作者：
R. Tunuguntla;D. Ripley;Q. Sang;N. Chegini
基质金属蛋白酶（MMPs）及其生理抑制剂组织抑制剂（TIMPs）在肿瘤细胞侵袭、血管生成和生长中起关键作用。本研究的目的是确定MMP-26、TIMP-3和TIMP-4在子宫内膜癌和良性子宫内膜中的表达和细胞分布，以及与肿瘤组织学亚型、分期和分级的相关性。TSMMP-26、TIMP-3和TIMP-4在来自月经周期的各个阶段的子宫内膜癌（N = 86）和良性子宫内膜（N = 50）中表达。染色强度的半定量分析表明，子宫内膜癌表达更多的MMP-26，TIMP-3和TIMP-4相比，良性子宫内膜从绝经后时期，但不是从分泌期的月经周期。染色强度最高的是子宫内膜上皮细胞，其次是血管内皮细胞、子宫肌层平滑肌细胞和子宫内膜间质细胞。MMP-26和TIMP-3的染色强度增加与III级肿瘤相关，MMP-26和TIMP-4与组织学特征为类神经胶质腺癌、透明细胞癌、和乳头状浆液性癌分期/分级的基础上FIGO标准。MMP-26和TIMP-4在子宫内膜和子宫内膜癌中表达，它们的表达升高以及与子宫肌层浸润的相关性表明MMP-26和TIMP-4在子宫内膜和子宫内膜癌中表达升高。4可能在子宫内膜肿瘤进展中发挥关键作用。
OBJECTIVEMatrix 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.METHODSImmunohistochemical 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.RESULTSMMP-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.CONCLUSIONMMP-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.