医学硕论-ZEB1和E-钙粘蛋白在乳腺癌中的表达及意义研究.doc

摘 要目的 研究E-钙粘蛋白（E-cadherin）以及转录因子ZEB1在乳腺癌和癌旁组织中的表达情况对比研究E-钙粘蛋白以及转录因子ZEB1在乳腺癌中的表达情况与相关病理学因素临床病理学因素（年龄、肿块直径、病理组织学分类、组织学分级、TNM分期、淋巴结转移）之间的相互关系探讨E-钙粘蛋白以及转录因子ZEB1在乳腺癌中的表达与ER、PR、HER-2及Ki-67表达之间的关系并分析E-钙粘蛋白与ZEB1在乳腺癌表达的相互关联性进一步探索E-钙粘蛋白与ZEB1在乳腺癌发生发展的细胞分子生物学机制，为临床诊断和治疗乳腺癌提供一定的借鉴作用方法 采用免疫组织化学技术（超敏型S-P法）检测320例乳腺癌组织和80例乳腺癌旁组织中讨E-钙粘蛋白以及ZEB1的表达情况，对检测到的结果进行统计学分析，确定表达情况的差异是否具有统计学意义并运用统计学方法对E-钙粘蛋白以及ZEB1的表达情况与患者年龄、肿块直径、病理组织学分类、组织学分级、TNM分期、淋巴结转移、ER、PR、HER-2及Ki-67表达进行分析并分析E-钙粘蛋白与ZEB1表达之间的关联性结果 1. E-钙粘蛋白在80例乳腺癌旁组织中仅有2例呈阴性表达，阳性率为97.5%。

320例乳腺癌组织中E-cadherin阳性表达的有206例，阳性率为64.4%E-钙粘蛋白在乳腺癌组织中的表达较之乳腺癌来说相对较低，这些不同的差异从统计学来说具有重要的作用E-cadherin在乳腺癌中的表达与年龄、肿块直径、病理组织学分类、TNM分期、淋巴结转移显著相关（P<0.05），而与组织学分级无明显关联（P>0.05）乳腺癌中E-cadherin表达阳性率与ER表达阳性率之间呈正相关（r=0.215，P<0.05）；与PR、HER-2及Ki-67表达阳性率之间均无显著相关（P>0.05）2. ZEB1在80例乳腺癌旁组织中仅有1例呈阳性表达，阳性率为1.2%320例乳腺癌组织中ZEB1阳性表达的有79例，阳性率达24.7%在组织中表达上来看，ZEB1在乳腺癌旁组织很显然低于在乳腺癌组织，两者存在较大的差异，而且对统计学来说具有极大的作用除此之外，ZEB1在乳腺癌中的表达与病理组织学分类、组织学分级、淋巴结转移显著相关（P<0.05），而与年龄、肿块直径、TNM分期无明显关联（P>0.05）在乳腺癌中ZEB1表达阳性率与HER-2表达阳性率之间呈正相关（r=0.115，P<0.05），与Ki-67表达阳性率之间呈正相关（r=0.141，P<0.05），与ER及PR表达阳性率之间无显著相关（P>0.05）。

3. 在乳腺癌中E-cadherin表达阳性率与ZEB1表达阳性率之间的关联性为呈负相关（r=-0.255，P<0.05）结论 E-钙粘蛋白在乳腺癌旁组织中广泛表达，但在乳腺癌组织中表达下调E-钙粘蛋白的表达伴随着乳腺癌肿块直径越大、TNM分期越高、淋巴结转移越多而降低，并与ER表达阳性率呈正相关提示在乳腺癌的发生和发展过程中，可能存在上皮-间质化，E-钙粘蛋白在乳腺癌的发生和发展过程中可能起到重要作用可以推断E-钙粘蛋白是关于乳腺癌非常有意义的生物学指标，通过检测E-钙粘蛋白的表达可为乳腺癌的临床诊断和预后判断提供借鉴参考1. ZEB1在乳腺癌旁组织中呈现低表达，而在乳腺癌组织中表达明显上调乳腺癌组织学分级越高、淋巴结转移越多，则ZEB1表达的阳性率越高，且ZEB1表达阳性率与HER-2、Ki-67表达阳性率之间呈正相关提示ZEB1的表达可能在乳腺癌的侵袭和转移的过程中发挥着重要作用可以推断在临床中检测ZEB1这项生物学指标，可以为诊断与治疗乳腺癌提供参考2. E-钙粘蛋白与ZEB1在乳腺癌中的表达具有关联性，E-钙粘蛋白表达阳性率与ZEB1表达阳性率之间呈负相关提示ZEB1可能参与上皮-间质化过程，ZEB1可能可以对乳腺癌中的E-钙粘蛋白表达进行调节。

本研究为乳腺癌的治疗提供了了新的思路，ZEB1可能成为乳腺癌治疗的新靶点关键词：乳腺癌，E-钙粘蛋白，ZEB1，免疫组织化学35ABSTRACTObjective To observe the expression of E-cadherin and transcription factor ZEB1 in breast cancer and the adjacent noncancerous tissues. To investigate the potential correlation between the expression of E-cadherin and ZEB1 in breast cancer with the clinicopathological features such as age, tumor size, histopathological classification, histological grade, TNM stage and lymph node metastasis. To explore the relationship between the expression of E-cadherin, ZEB1, ER, PR, HER-2 and Ki-67 in breast cancer. To further explore the possible molecular biological mechanism of E-cadherin and ZEB1 in the development of breast cancer, and to provide some reference in the clinical diagnosis and treatment of breast cancer.Methods Immunohistochemistry test was performed to detect the expression of E-cadherin and ZEB1 in 320 cases of breast cancer and 80 adjacent noncancerous tissues. The results were analyzed to determine whether the differences was statistically significant. The association was analyzed on the expression between E-cadherin as well as ZEB1 with clinicopathological features such as age, tumor size, histopathological classification, histological grade, TNM stage, lymph node metastasis, ER, PR, HER-2 and Ki-67. We also analyzed the relationship between the expression of E-cadherin and ZEB1 in breast cancer.Results 1. In 80 cases of adjacent noncancerous tissues, only 2 cases were negatively expressed in E-cadherin, the positive rate was 97.5%. In 320 cases of breast cancer tissues, 206 cases were positively expressed in E-cadherin, the positive rate was 64.4%. The expression of E-cadherin in breast cancer was significantly lower than that in adjacent noncancerous tissues (P<0.001). The expression of E-cadherin in breast cancer was significantly correlated with age, tumor size, histological classification, TNM stage and lymph node metastasis (P<0.05), but not with histological grade (P>0.05). There was a positive correlation between the expression of E-cadherin with ER (r=0.215, P<0.05), but no correlation between the expression of PR、HER-2 and Ki-67 in breast cancer (P>0.05).2. In 80 cases of adjacent noncancerous tissues, only 1 cases were positively expressed in ZEB1, the positive rate was 1.2%. In 320 cases of breast cancer tissues, 79 cases were positively expressed in ZEB1, the positive rate was 24.7%. The expression of ZEB1 in breast cancer was significantly higher than that in adjacent noncancerous tissues (P<0.001). The expression of ZEB1 in breast cancer was significantly correlated with histological classification, histological grade and lymph node metastasis (P<0.05), but not with age, tumor size and TNM stage (P>0.05). There was a positive correlation between the expression of ZEB1 with HER-2 (r=0.115, P<0.05) and Ki-67 (r=0.141, P<0.05), but no correlation with the expression of PR and ER in breast cancer (P>0.05).3. There was a negative correlation between the expression of E-cadherin and ZEB1 in breast cancer (r=-0.255, P<0.05).Conclusion 1. E-cadherin is widely expressed in adjacent noncancerous tissues, but down-regulated in breast cancer tissues. The level of its expression was related to the tumor size, histological classification, TNM stage and lymph nod。