乳腺癌组织中MMP-2、TIMP-2、TGF-β_1、TGF-β_1RⅠ的表达及相关性分析

Expression of MMP-2,TIMP-2,TGF-β_1,TGF-β_1RI and its relationship in breast cancer

目的探讨基质金属蛋白酶(MMP)-2及其抑制物(TIMP-2)与转化生长因子(TGF)-β1及其I型受体(TGF-β1RI)在乳腺癌组织中的表达及其相关性。方法应用免疫组化SP法检测80例乳腺癌组织中的MMP-2、TIMP-2与TGF-β1、TGF-β1RI蛋白。结果乳腺癌中MMP-2、TIMP-2、TGF-β1和TGF-β1RI阳性表达率分别为67.5%、45.0%、80.0%和67.5%;无淋巴结转移者MMP-2、TIMP-2阳性表达率为44.4%、66.7%,与转移淋巴结个数1～3(85.7%、21.4%)、>3个(87.5%、37.5%)相比,P均<0.01;TNM分期为Ⅰ期的MMP-2、TIMP-2阳性表达率分别为0、75%,分别与Ⅱ(65.0%、55.0%)、Ⅲ(86.7%、26.7%)、Ⅳ期(100%、0)相比,P均<0.05;肿瘤直径≤2cm者TIMP-2阳性表达率为66.7%,与直径2～5(51.9%)、>5cm(20.0%)相比,P均<0.05;MMP-2和TGF-β1的表达呈正相关(r=0.454,P<0.01),MMP-2和TGF-β1RI的表达呈负相关(r=-0.481,P<0.01)。结论MMP-2和TIMP-2的表达情况与乳腺癌侵袭转移有密切关系。MMP-2的表达与TGF-β1、TGF-β1RI关系密切,MMP-2可能在一定程度上受到TGF-β及其受体的调控。

Objective To investigate the expression of MMP-2, TIMP-2, TGF-β1 and TGF-β1 RⅠ, its relationship in breast cancer. Methods The MMP-2, TIMP-2, TGF-β1 and TGF-β1 RⅠ were examinated in 80 cases of breast carcinoma by SP immunohistochemical method. Results The positive rates of MMP-2, TIMP-2, TGF-β1 and TGF-β1RⅠ were 67. 5% ,45.0% ,80.0% and 67.5%, respectively. The expression of MMP-2 was positively correlated to axillary lymph node metastasis and TNM staging（ P 〈0.01 and P 〈0. 01, respectively）. The expression of TIMP-2 was positively correlated to tumor size, axillary lymph node metastasis （ P 〈 0. 05, P 〈 0.01, respectively）. The expression of MMP-2 was positively correlated to that of TGF-β1 （ r = 0. 454, P 〈 0. 01 ） , and was negatively correlated to that of TGF-β1 RⅠ （ r = - 0.481, P 〈 0.01 ）. Conclusions The expression of MMP-2 and TIMP-2 might be close correlated to the invasion and metastasis of breast cancer. The expression of MMP-9 has a close relationship with TGF-β1 and TGF-β1 RⅠ. The levels of MMP-9 might be partly regulated by TGF-β1 and TGF-β1RⅠ.