膀胱癌中锌指结构转录因子1和E钙黏蛋白的表达及其相关性研究

The expression and correlation of ZEB 1 and E-cadherin in human bladder urothelial carcinoma

目的 探讨锌指结构转录因子1（zinc finger E-box binding homeobox 1,ZEB1）和E钙黏蛋白在膀胱尿路上皮癌组织和正常膀胱黏膜组织中的表达情况、相关性及其与临床病理特征的关系.方法 收集2008年3月至2011年3月86例膀胱尿路上皮癌患者的手术标本.男51例,女35例.年龄36 ～72岁,平均（64.1±10.2）岁.其中＞65岁40例,≤65岁46例.均经病理检查证实为膀胱尿路上皮癌,病理分级：G128例,G2～G358例.TNM分期：Ta～T1期34例,T2～T4期52例.肿瘤单发49例,多发37例.初发55例,复发31例.16例正常膀胱黏膜组织取自BPH患者开放手术标本.年龄51 ～75岁,平均（58.6±18.4）岁.采用免疫组化染色方法分别检测ZEB1和E钙黏蛋白在膀胱癌组织及正常膀胱黏膜组织中的表达情况,分析两者在膀胱癌组织中表达的相关性,以及两者表达情况与患者临床病理特征的关系.结果 ZEB1在膀胱癌组织和正常膀胱黏膜组织中表达的阳性率分别为39.5％（34/86）和0（0/16）;在高分级（G2 ～ G3）和低分级（G1）膀胱癌组织中表达的阳性率分别为48.3％（28/58）和21.4％（6/28）;在T2～T4期和Ta～T1期膀胱癌组织中表达的阳性率分别为51.9％ （27/52）和20.6％（7/34）,差异均有统计学意义（P＜0.05）.E钙黏蛋白在膀胱癌组织和正常膀胱黏膜组织中表达的异常率分别为61.6％ （53/86）和81.2％（13/16）,差异有统计学意义（P＜0.01）;在高分级（G2 ～ G3）和低分级（G1）膀胱癌组织中表达的异常率分别为53.4％（31/58）和78.6％（22/28）;在T2～ T4期和Ta～T1期膀胱癌组织中表达的异常率分别为51.9％（27/52）和76.5％（26/34）,差异均有统计学意义（P＜0.05）.在膀胱癌组织中,ZEB1的阳性表达与E钙黏蛋白的异常表达间呈负相关（r =0.247,P＜0.05）.结论 ZEB1和E钙黏蛋白在膀胱癌组织中的表达具有负相关性,且两者的表达与膀胱癌的分期、分级密切相关.

Objective To explore the expression,correlation and clinic-pathological characters of zinc finger E-box binding homeobox 1 （ZEB1） and E-cadherin in normal bladder tissues and bladder urothelial carcinoma（BUC）.Methods Immunohistochemical staining was performed on paraffin embedded sections to detect the expression of ZEB1 and E-cadherin in 86 cases of BUC,diagnosed by pathology,between March 2008 and March 2011.Among them,51 cases were male and 35 cases were female.The mean age was （64.1 ± 10.2）years,range 36 to 72 years.40 cases were older than 65 years old,and 46 cases were less than 65 years old.The pathological classification included G1 in 28 cases,G2-G3 in 58 cases.The TNM classification showed that Ta-T1 stage in 34 cases,T2-T4 in 52 cases.Single lesion was found in 49 cases and multi lesion was found in 37 cases.55 cases were primary lesion;the other 31 cases were diagnosed as tumor recurrence.Normal bladder mucosa was obtained from 16 patients with BPH.Their age ranged from 51 to 75 years old,mean （58.6 ± 18.4） years old.Similar immunohistochemical staining about ZEB1 and E-cadherin was performed.The expression of ZEB1 and E-cadherin in different tissue and its relationship with the clinic pathological were further analyzed.Results The positive rate of ZEB1 in bladder cancer group （39.5%,34/86） was significantly higher than that in normal bladder mucosa group （0,0/16） （P 〈 0.01）.The positive rate of ZEB1 in high grade bladder cancer （G2-G3） was 48.3% （28/58）,which was significant higher than that in low grade bladder cancer （G1） （21.4%,6/28） （P 〈0.05）;The positive rate of ZEB1 in muscle-invasive bladder cancer （T2-T4） was 51.9% （27/52）,which was significant higher than that in non-muscle-invasive cancer （Ta-T1） （20.6%,7/34） （P 〈 0.01）.The abnormal rate of E-cadherin expression in bladder cancer （61.6%,53/86） was significantly lower than that in normal bladder mueosa （81.2%,13/16） （P 〈 0.01）.The abnormal expression rate of E-cadherin in high grade bladder cancer （G2-G3） （53.4%,31/58） was significantly lower than that in low grade bladder cancer （G1） （78.6%,22/28）（P 〈 0.05）;The abnormal rate of E-cadherin expression in invasive bladder cancer （T2-T,4） was 51.9% （27/52）,which was lower than that in non-muscle invasive （Ta-T1） cancer （76.5%,26/34） （P 〈 0.05）.In bladder cancer,there was a negative correlation between the abnormal expression of E-cadherin and positive expression of ZEB1 （r =0.247,P 〈 0.05）.Conclusion The expressions of ZEB1 and E-cadherin in bladder cancer were negatively correlated,which had high correlated with tumor grade and stage.