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

Abstract

To investigate the significance of CD99 protein expression and gene promoter hypermethylation status in urinary bladder carcinoma and its correlation with the histopathologic parameters. CD99 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. The 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. The 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.