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

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, MMP-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）；HMGA2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 group AT-hook 2 (HMGA2) and matrix metalloproteinase-1 (MMP-11) in breast cancer tissue and their clinical 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 cancer tissues and pericarcinomatous tissues. The correlation of HMGA2, MMP-11 expression with the clinicopathological features and prognosis of breast cancer patients was analyzed. Results The positive expression 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). The expression 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 noses metastasis (P＜0.001), negative estrogen receptor (ER) expression (P=0.017), positive HER-2 expression (P＜0.001), and Ⅲ-Ⅳ stage in TNM classification (P=0.013). The expression of MMP-11 was 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 TNM classification (P=0.001). There was a significant association between overexpression of HMGA2 and expression of MMP-11 in breast cancer tissues (r=0.772，P＜0.01). Univariate analysis showed that the disease free survival (DFS) and overall survival (OS) among the HMGA2 and MMP-11 positive group was worse compared to HMGA2 and/or MMP-11 negative groups and the