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(matrix metalloproteinases, MMPs)-2、9及其组织抑制因子(tissue inhibitor of metalloproteinases, 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%、20%及67%,高于G2(13%、0及27%)、G1者(均为0,P<0.05);深肌层浸润内膜癌的强阳性率分别为63%、16%及68%,高于浅肌层浸润的8%、0及0(P<0.01);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25%、0及25%(P<0.05);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<0.05);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胞中的表达率比较,差异均无显著性(P>0.05).内膜癌血管内皮细胞中,MMP-2及TIMP-1蛋白的表达,病理分级为G3内膜癌的强阳性率均为60%,高于G2(均为20%)及G1者(均为7例中1例,P<0.05).内膜癌细胞及血管内皮细胞中,MMP-2、MMP-9及TIMP-1、TIMP-2蛋白的强阳性率均高于绝经期内膜,差异有显著性(P<0.05).明胶酶谱测定结果显示,内膜癌组织中MMP-2蛋白的活性较MMP-9蛋白强,且主要以活性形式存在.结论 MMP-2、MMP-9蛋白在内膜癌中的表达随病理分级的升高、肌层浸润程度的加深及有淋巴结转移而增加;MMP-2蛋白的活性较MMP-9蛋白强, 且主要以活性形式存在.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.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.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 grade II (13%, 0, 27%) and grade I (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 grade II (20%) and grade I (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.MMP-2 and MMP-9 expression levels in adenocarcinoma tissue correlate with the histologic grade and invasion/metastasis trend. Active MMP-2 is the main form in endometrial cancer.PubMed中文核心期刊要目总览(PKU)中国科学引文数据库(CSCD)010604-6073