上皮间质转化分子标记物在乳腺浸润性导管癌组织中的表达及临床意义

目的 探讨乳腺浸润性导管癌组织中上皮间质转化（EMT）分子标记物E 钙黏蛋白、N 钙黏蛋白、基质金属蛋白酶9（MMP 9）和MDM2蛋白的表达及其与临床病理特征和预后的关系。方法 应用免疫组织化学法检测242例乳腺浸润性导管癌患者手术标本中E 钙黏蛋白、N 钙黏蛋白、MMP 9和MDM2蛋白的表达水平，并进行统计分析。结果在乳腺浸润性导管癌组织中，E 钙黏蛋白、N 钙黏蛋白、MMP 9和MDM2的阳性表达率分别为70.7％、2.9％、54.9％和49.6％，其中，E-钙黏蛋白与MMP-9的表达呈正相关（r=0.238，P=0.000），MDM2与MMP-9的表达也呈正相关（r=0.171，P=0.012）。E-钙黏蛋白的表达与肿瘤大小及雌激素受体（ER）状态有关，肿瘤较小及ER阳性者的E-钙黏蛋白阳性表达率高；MDM2的表达与肿瘤大小也存在显著相关性（P=0.028），肿瘤较小者的MDM2阳性表达率高。生存分析显示，肿瘤较大、淋巴结转移及MDM2表达阳性者的术后无病生存期较短，其中淋巴结转移（HR=11.33，95％CI：3.46～37.13，P＜0.001）和MDM2表达阳性（HR=5.17，95％CI：1.66～16.10，P=0.005）是乳腺浸润性导管癌患者的独立不良预后因素。结论 MDM2是乳腺浸润性导管癌的不良预后因子之一，MDM2可能通过上调MMP-9的表达，介导EMT发生，导致肿瘤浸润转移影响预后。

Expression and clinical significance of epithelial-mesenchymal transition biomarkers in infiltrating ductal breast cancer

Objective To detect the expression of epithelial-mesenchymal transition （EMT） biomarkers including E-cadher- in, N-eadherin, matrix metalloproteinase （MMP）-9 and MDM2 in infiltrating ductal breast cancer （IDBC） tissues, and evaluate the correlation between the expression levels of these proteins and elinicopathological features, as well as the prognosis of IDBC. Methods Two hundred and forty-two IDBC specimens were detected for E-cadherin, N-cadherin, MMP-9 and MDM2 expression by immuno- histochemistry （IHC）. Patients were followed up and statistical analysis was performed with SPSS 17.0. Results Positive rates of E- cadherin, N-cadherin, MMP-9 and MDM2 in IDBC tissues were 70. 7% , 2. 9% , 54. 9% and 49. 6% , respectively. A significant cor- relation was confirmed between the expression of MMP-9 and E-cadherin （r =0. 238, P =0. 000） , or between MDM2 and MMP-9 （r =0. 171, P = 0. 012）. Tumor size was significantly associated with the expression of E-eadherin （P = 0. 017） and MDM2 （P = 0. 028 ）. In addition, estrogen receptor （ER） status was significantly associated with E-cadherin expression （P = 0. 010）. Univariate analysis showed a significant association between tumor size, lymph node in volvement, MDM2 expression and disease-free survival （P 〈 O. 05 ） , but not E-cadherin, N-cadherin or MMP-9 showed a marked effect on disease-free survival. Muhivariate analysis revealed that lymph node involvement （HR = 11.33, 95%CI：3.46-37. 13, P 〈0. 001） , and MDM2 expression （HR =5. 17, 95% CI：l. 66- 16. 10, P =0. 005 ） were independent unfavourable prognostic factors for IDBC. Conclusion MDM2 is an independent unfavorable prognostic factor for IDBC. MDM2 might induce EMT by up-regulating expression of MMP-9, and then resuh in tumor invasion and metastasis.