Significance of TWIST expression and its association with E-cadherin in bladder cancer

Hum Pathol. 2007 Apr;38(4):598-606. doi: 10.1016/j.humpath.2006.10.004. Epub 2007 Jan 29.


Recently, TWIST, a basic helix-loop-helix transcription factor, has been reported to play a key role in the metastatic progression of several types of human cancer. The aim of this study was to investigate the significance of TWIST expression in bladder cancer using tissue microassays generated from 226 bladder tissue specimens. Using immunohistochemical staining, we studied TWIST expression levels in nonmalignant bladder tissues (n = 37), primary bladder cancer tissues (n = 164), and 25 cases of matched lymph node metastatic lesions. The association between TWIST expression levels and tumor staging and grading, as well as metastatic potential, was analyzed by statistical analysis. Our results showed that TWIST protein expression was significantly higher in bladder cancer specimens compared with nonmalignant tissues (P < .001), indicating its positive role in the development of bladder cancer. In addition, increased TWIST expression levels were associated with advanced-stage and high-grade tumors, suggesting its involvement in the progression of this cancer. Furthermore, TWIST expression was much higher in the metastatic lesion compared with its primary site (P < .05). More importantly, the increased TWIST expression in bladder cancer specimens was correlated with decreased membranous expression of E-cadherin, a cell adhesion molecule that plays a key role in the metastatic progression of human cancer. Our results demonstrate TWIST as a novel positive factor in the development and progression of bladder cancer and suggest a marker for advanced bladder cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Cadherins / biosynthesis*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / physiopathology
  • Male
  • Middle Aged
  • Nuclear Proteins / biosynthesis*
  • RNA, Messenger / metabolism
  • Twist-Related Protein 1 / biosynthesis*
  • Up-Regulation
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*


  • Biomarkers, Tumor
  • Cadherins
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Twist-Related Protein 1