【作者】 吴正升；

【导师】 吴强； 孟刚；

【作者基本信息】 安徽医科大学 ， 病理学与病理生理学， 2005， 硕士

【摘要】 目的:检测乳腺癌、乳腺良性病变组织中明胶酶(MMP-2、MMP-9)及其抑制因子(TIMP-1、TIMP-2)蛋白质和mRNA水平的表达,并检测患者术前血清MMP-9、TIMP-1蛋白浓度,观察它们与乳腺癌临床病理特征的关系,探讨明胶酶及其抑制因子在乳腺癌发生、侵袭转移中的生物学意义及临床应用价值。方法:采用组织微阵列平台,应用免疫组织化学S-P法检测20例乳腺良性病变组织、160例浸润性乳腺癌组织MMP-2、MMP-9、TIMP-1和TIMP-2蛋白表达,原位分子杂交技术检测MMP-9、TIMP-1 mRNA表达;使用ELISA技术检测其中9例乳腺良性病变、29例浸润性乳腺癌患者术前血清MMP-9和TIMP-1的蛋白浓度。结果:1.乳腺癌组织MMP-2、MMP-9、TIMP-1和TIMP-2的蛋白表达以及MMP-9、TIMP-1的mRNA表达均较良性病变组织显著增强;乳腺癌患者术前血清MMP-9、TIMP-1浓度均显著高于乳腺良性病变组。2.乳腺癌组织MMP-2、MMP-9蛋白表达和MMP-9/TIMP-1、MMP-2/TIMP-2蛋白表达比值均与腋淋巴结受累、TNM分期呈正相关;TIMP-2蛋白表达与腋淋巴结受累呈负相关。3.乳腺癌组织MMP-9mRNA表达和MMP-9/TIMP-1 mRNA表达比值与腋淋巴结受累、TNM分期均呈正相关;TIMP-1 mRNA表达与组织学分级呈负相关。4.乳腺癌患者术前血清MMP-9浓度、MMP-9/TIMP-1比值均与腋淋巴结受累、TNM分期呈正相关;TIMP-1浓度与腋淋巴结受累呈正相关。5.乳腺癌组织MMP-2和TIMP-2蛋白表达、MMP-9和TIMP-1蛋白表达、MMP-9和TIMP-1 mRNA表达均呈显著正相关。6.乳腺癌患者术前血清MMP-9、TIMP-1浓度与组织中相应蛋白表达均呈正相关。结论:1.MMP-2、MMP-9、TIMP-1和TIMP-2的整体表达上调与乳腺癌发生过程有关;在乳腺癌中可能存在着明胶酶及其抑制因子的反馈调节网络,它们共同参与了乳腺癌的发生。2.明胶酶及其抑制因子在乳腺癌的侵袭转移中发挥了重要作更多还原

【Abstract】 Objective To detect the protein and mRNA expression of gelatinase (MMP-2, MMP-9) and its inhibitors (TIMP-1, TIMP-2) in tissues from breast carcinoma and benign diseases, and to detect the concentrations of MMP-9 and TIMP-1 in patient’s preoperative serum. To investigate their roles in carcinogenesis, tumor invasion and metastasis and to evaluate their clinicopathologic significances. Methods The protein expression of MMP-2, MMP-9, TIMP-1, TIMP-2 and the mRNA expression of MMP-9 and TIMP-1 were examined by immunohistochemistry S-P method and in situ hybridization technique respectively in 20 cases of breast benign diseases and 160 cases of infiltrating carcinoma tissues on tissue microarray platform. Among those cases, the preoperative serum concentrations of MMP-9 and TIMP-1 were detected by sandwich ELISA technique in 9 cases of breast benign diseases and 29 cases of breast infiltrating carcinoma. Results 1. The protein expression of MMP-2, MMP-9, TIMP-1, TIMP-2 and mRNA expression of MMP-9, TIMP-1 in breast carcinoma were significantly higher than those in breast benign diseases. The patient’s preoperative serum concentrations of MMP-9 and TIMP-1 were significantly higher in breast carcinoma than those with breast benign diseases. 2. The protein expression of MMP-2, MMP-9 and the ratios of MMP-9 to TIMP-1 and MMP-2 to TIMP-2 were all positively correlated to TNM staging and lymph node metastasis. The protein expression of TIMP-2 was negatively correlated to lymph node metastasis. 3. Both the mRNA expression of MMP-9 and the ratio of MMP-9 to TIMP-1 were positively correlated to TNM staging and lymph node metastasis. The mRNA expression of TIMP-1 was negatively correlated to histological grading of breast carcinoma. 4. Both the patients’更多还原