Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder

Protein expression and gene promoter hypermethylation of CD99 in transitional cell carcinoma of urinary bladder
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膀胱移行细胞癌中CD99蛋白表达及基因启动子高甲基化

DOI:
10.1007/s00432-010-0858-z
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发表时间:
2010
影响因子:
3.6
通讯作者:
Lin, Zhenhua
Lin, Zhenhua
中科院分区:
医学3区
文献类型:
--
作者:
Xuan, Yanhua;Kim, Seokhyung;Lin, Zhenhua

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为探讨膀胱癌组织中CD 99蛋白表达及基因启动子区甲基化状态与膀胱癌病理学参数的关系,采用免疫组织化学方法检测100例膀胱移行细胞癌(TCC)和35例正常膀胱组织中CD 99蛋白的表达,结果膀胱移行细胞癌组织中CD 99蛋白阳性表达率为62%(62/100),低于正常膀胱粘膜组织中的97.1%(34/35)。CD 99基因启动子区甲基化阳性率为31.7%(26/82),10例正常膀胱移行上皮组织中均未检测到CD 99基因启动子区甲基化。膀胱移行细胞癌中CD 99甲基化与CD 99蛋白表达下调显著相关(P< 0.001)。膀胱移行细胞癌中CD 99蛋白表达降低和甲基化频率增高与膀胱移行细胞癌的临床分期、病理分期和组织学分级密切相关。结论膀胱移行细胞癌中CD 99蛋白表达下调是膀胱移行细胞癌发生发展的重要因素,尤其是在晚期,其原因可能与膀胱移行细胞癌中CD 99基因启动子区甲基化有关。CD 99蛋白表达和基因启动子甲基化对膀胱移行细胞癌的诊断和靶向治疗具有临床意义。
PurposesTo investigate the significance of CD99 protein expression and gene promoter hypermethylation status in urinary bladder carcinoma and its correlation with the histopathologic parameters.Materials and methodsCD99 protein expression was determined by immunohistochemical staining in a series of 100 cases of transitional cell carcinomas (TCC) and 35 cases of normal urinary bladder tissues, and the methylation status of CD99 gene promoter was studied by using methylation-specific PCR and DNA sequencing.ResultsThe positive rate of CD99 protein expression was 62% (62/100) in TCC tissues, it was lower than in normal urinary bladder epithelia (97.1%, 34/35). Gene promoter hypermethylation of CD99 was observed in 26 of 82 (31.7%) cases, and none of the detected ten cases of normal transitional epithelia tissues showed CD99 methylation. CD99 hypermethylation was significantly associated with CD99 protein down-regulation in TCC (P< 0.001). Both the decreased protein expression and the higher methylated frequency of CD99 in TCC of urinary bladder were significantly correlated with the clinical stage, pathological stage, and histological grade.ConclusionsThe down-regulation of CD99 protein expression is a critical event in the progress of TCC, especially in advanced stage, and it can be explained by the presence of CD99 gene promoter hypermethylation in TCC. And both CD99 protein expression and gene promoter hypermethylation have clinical significance and implication for the diagnosis and target therapy for TCC.
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