高迁移率族蛋白A2和基质金属蛋白酶-11在乳腺癌组织中的表达与预后的关系

Expression of high mobility group AT-hooks 2 and matrix metalloproteinase-11 in breast cancer tissue and their clinical significance

目的探讨高迁移率族蛋白A2(high mobility group AT-hook 2,HMGA2)和基质金属蛋白酶-11(matrix metalloproteinase-1,M M P-11)在乳腺癌组织中的表达及意义。方法收集173例女性乳腺癌患者的临床病理资料,采用免疫组织化学法,对乳腺癌组织和癌旁组织中的HMGA2和MMP-11进行检测,分析两者表达与乳腺癌病理参数之间的关系,并评价两者表达与乳腺癌预后的关系。结果乳腺癌组织中HMGA2和MMP-11阳性表达率分别为74.6%(129/173)、59.0%(102/173),明显高于癌旁组织(P<0.001);HM GA2阳性表达与患者年龄>40岁(P=0.044)、绝经后(P=0.046)、组织学分级Ⅲ级(P=0.024)、腋窝淋巴结转移(P<0.001)、雌激素受体(estrogen receptor,ER)阴性表达(P=0.017)、HER-2阳性表达(P<0.001)和TNM分期Ⅲ~Ⅳ期(P=0.013)显著相关;MMP-11阳性表达与腋窝淋巴结转移(P=0.001)、ER阴性表达(P<0.001)、HER-2阳性表达(P=0.021)和TNM分期Ⅲ~Ⅳ期(P=0.001)显著相关;HMGA2阳性表达与MMP-11阳性表达呈正相关(r=0.772,P<0.01)。单因素分析显示,HMGA2和MMP-11表达阳性者的无病生存时间(disease free survival,DFS)和总生存时间(overall survival,OS)均较HMGA2和/或MMP-11表达阴性组差(DFS:P=0.001;OS:P<0.001)。多因素Cox分析表明,HMGA2(P=0.002)和MMP-11(P=0.022)是影响乳腺癌患者DFS的独立预后因素;HMGA2情况是影响乳腺癌患者OS的独立预后因素(P=0.001)。结论 HMGA2和MMP-11在乳腺癌组织中表达上调并存在相关性,HMGA2和MMP-11表达阳性提示患者预后不良,两者可能成为潜在的判断乳腺癌预后的分子标志物。

Objective To investigate the relationship between the expression of high mobility groupAT.hook 2 （HMGA2） and matrix metalloproteinase-1 （MMP-11） in breast cancer tissue and theirclinical significance. Methods Clinicopathology data of 173 patients with breast cancer were studied.Immunohistochemical method was used to detect the expression of HMGA2 and MMP-11 in breast cancertissues and pericarcinomatous tissues. The correlation of HMGA2, MMP.11 expression with theclinicopathological features and prognosis of breast cancer patients was analyzed. Results The positiveexpression rate of HMGA2 and MMP.11 in breast cancer tissues was 74. 6% （129/ 173） and 59. 0% （102/ 173）, which was significantly higher than that in pericarcinomatous tissues （ P 〈 0. 001）. Theexpression of HMGA2 was significantly upregulated in breast cancer patients with age over 40 yeas （P=0. 044）, postmenopause （P = 0. 046）, higher histological grade （P = 0. 024）, axillary lymph nosesmetastasis （P 〈 0. 001）, negative estrogen receptor （ ER） expression （ P = 0. 017）, positive HER.2expression （P〈0. 001）, and Ⅲ.Ⅳ stage in TNM classification （P = 0. 013）. The expression of MMP.11was significantly upregulated in breast cancer patients with axillary lymph noses metastasis （P= 0. 001）,negative ER expression （P〈0. 001）, positive HER.2 expression （P = 0. 021）, and Ⅲ.Ⅳ stage in TNMclassification （P = 0. 001）. There was a significant association between overexpression of HMGA2 andexpression of MMP.11 in breast cancer tissues （r= 0. 772,P〈0. 01）. Univariate analysis showed that thedisease free survival （DFS） and overall survival （OS） among the HMGA2 and MMP-11 positive groupwas worse compared to HMGA2 and / or MMP-11 negative groups and the difference were significant（DFS： P = 0. 001; OS： P〈0. 001）. Multivariate analysis showed that the expression status of HMGA2（P= 0. 002）. and MMP.11 （P = 0. 022） were independent prognostic factors of DFS and HMGA2 wasindependent prognostic factor of OS （P= 0. 001）. Conclusion There was correlation between HMGA2and MMP-11 expression in breast cancer. The expression of HMGA2 and MMP-11 may serve as potentialbiomarkers for poorer prognosis for breast cancer.