基质金属蛋白酶及其组织抑制因子在子宫内膜癌中的表达及其意义

Expression of matrix metalloproteinase-2,9 and it′s tissue inhibitor-1,2 in endometrial carcinoma

目的 研究基质金属蛋白酶 (matrixmetalloproteinases,MMPs) 2、9及其组织抑制因子(tissueinhibitorofmetalloproteinases ,TIMPs) 1、2在子宫内膜癌中的表达 ,探讨其与子宫内膜癌浸润转移的关系。方法 应用链霉菌抗生物素蛋白 过氧化物酶免疫组织化学方法和明胶酶谱法对 37例内膜癌及 7例绝经期妇女子宫内膜组织中MMP 2、MMP 9、TIMP 1、TIMP 2蛋白及其活性进行检测。结果 MMP 2、MMP 9及TIMP 1、TIMP 2蛋白主要分布在内膜癌细胞、血管内皮细胞及绝经期子宫内膜腺上皮细胞中 ,在间质细胞中也有少量表达。内膜癌细胞中 ,MMP 2、MMP 9及TIMP 1蛋白的表达 ,病理分级为G3内膜癌的强阳性率分别为 73%、2 0 %及 6 7% ,高于G2 (13%、0及 2 7% )、G1 者 (均为 0 ,P<0 0 5 ) ;深肌层浸润内膜癌的强阳性率分别为 6 3%、16 %及 6 8% ,高于浅肌层浸润的 8%、0及 0 (P<0 0 1) ;有淋巴结转移者的强阳性率分别为 4例中 4例、4例中 3例及 4例中 4例 ,高于无淋巴结转移者的 2 5 %、0及 2 5 % (P <0 0 5 ) ;手术病理分期为Ⅲ～Ⅳ期者强阳性率分别为 5例中 5例、5例中 3例及 5例中 5例 ,高于Ⅰ～Ⅱ期者的 30 %、0及 30 % (P <0 0 5 ) ;TIMP 2蛋白在不同病理分级、肌层浸润、淋巴结转移和手术病理分期的内膜癌细?

Objective To study the expression of matrix metalloproteinase(MMP)-2,9 and tissue inhibitor of metalloproteinase(TIMP)-1,2 protein in human endometrial carcinoma tissue and its relation to the invasion and metastasis of endometrial carcinoma. Methods Immunocytochemistry and zymography techniques were used to measure the MMP-2,MMP-9,TIMP-1,TIMP-2 protein levels and activities in endometrial carcinoma tissue of 37 patients and control group composed of 7 normal postmenstrual endometrial samples. Results The MMP-2,MMP-9,TIMP-1 and TIMP-2 proteins mainly expressed in endometrial carcinoma cells, glandular cells and endothelial cells. The strongly positive expression proportions of MMP-2,9 and TIMP-1 proteins in grade Ⅲ carcinoma cells were respectively 73%, 20% and 67%, which were higher than those in gradeⅡ (13%, 0, 27%) and gradeⅠ (0) ones ( P <0.05). They were also higher in endometrial carcinoma with deep layer invasion ones (63%, 16%, 68%) and lymph node metastasis ones (4/4, 3/4, 4/4). TIMP-2 did not show different expression with the tumor invasion and metastasis. In endothelial cells of grade Ⅲ carcinoma tissue the strongly positive expression proportions of MMP-2 (60%) and TIMP-1 (60%) proteins, not MMP-9, were found in higher amount comparing with those in gradeⅡ (20%) and gradeⅠ (1/7) tumor tissues ( P <0.05). The density of above four proteins were all found very low in the normal postmenopausal endometrial tissues ( P <0.05). By zymography test the active MMP-2 was the main protein form in adenocarcinoma tissue. Conclusions MMP-2 and MMP-9 expressionlevels in adenocarcinoma tissue correlate with the histologic grade and invasion/metastasis trend. Active MMP-2 is the main form in endometrial cancer.