MMP-2、MMP-9、TIMP-1和TIMP-2在乳腺癌中的表达及临床意义

Expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in breast carcinomas and their clinical significance

目的 研究MMP 2、MMP 9、TIMP 1和TIMP 2在乳腺癌中的表达及与临床病理特征的关系。方法 免疫组化SP法检测 66例原发性乳腺癌、1 3例乳腺纤维腺瘤和 1 5例乳腺纤维腺病中的蛋白表达。结果 ①乳腺癌中MMP 2、MMP 9的阳性表达显著高于乳腺纤维腺瘤和纤维腺病 (P <0 0 5) ;②MMP 9的阳性表达与乳腺癌肿瘤大小、临床分期呈正相关 (P <0 0 5) ,伴腋窝淋巴结转移的乳腺癌中MMP 9、MMP 2呈高表达 ,但TIMP 1显著低表达 ;乳腺癌中MMP 9与TIMP 1的表达呈负相关 (P <0 0 5) ;③MMP 2、MMP 9表达的乳腺癌患者预后差。结论 乳腺癌中MMP 2、MMP 9表达显著高于乳腺良性病变 ;

Objective To study the expression and prognosti c significance of matrix metalloproteinase 2 protein (MMP-2), matrix metalloprot einase 9 protein (MMP-9), tissue inhibitor of matrix metalloproteinase 1 prot ein (TIMP-1) and tissue inhibitor of matrix metalloproteinase 2 protein (TIMP -2) in the breast carcinomas and benign breast diseases Methods Total 66 cases of breast cancers with follow-up, 13 breast fibroadenoma a nd 15 breast fibroadenomatosis were investigated by immunohistochemical staining with anti MMP-2, MMP-9, anti TIMP-1 and TIMP-2 monoclonal antibodies Results The expr ession of MMP-2 and MMP-9 was significantly higher in the breast cancers than those of breast fibroadenoma and fibroadenomatosis (P<0 05) There was a positive association between the expression of MMP-9 and size of the breast can cer, short survival time and TNM classification respectively (P<0 05). Ove rexpression of MMP-2 and MMP-9 in the breast cancers with axillary lymph node involvement was significantly higher than that without node metastases (P<0 05), but overexpression of TIMP-1 was reverse (P<0 05) Negative corre lation between expression of TIMP-1 and that of MMP-9 in breast cancer was obs erved (P<0 05). In both life tables and monovariate Kaplan-Meir plot anal ysis, expression of MMP-2 and MMP-9 proteins was correlated with unfavorable p rognosis Conclusions High activities of MMP-2 and MMP-9 en hances the tumor growth and the capacity to invade locally and metastasize Fur thermore, MMP-2 and MMP-9 proteins associate strongly with a shorted survival, and act as prognostic markers for patients with breast cancer after operation