Differential expression of progression-related genes in the evolution of superficial to invasive transitional cell carcinoma of the bladder

Oncol Rep. Jan-Feb 2001;8(1):9-15. doi: 10.3892/or.8.1.9.


It is generally accepted that there are dichotomous biologic pathways that lead to the development of either: i) superficial papillary (Ta) transitional cell carcinoma (TCC) or ii) precursor lesions to muscle-invasive (CIS, T1) TCC and muscle-invasive (> or =T2) TCC. We investigated the expression of several progression-related genes to characterize the phenotype of these tumors within these divergent developmental pathways. Using a colorimetric in situ hybridization technique, we examined the expression of mRNAs of several progression-related genes in archival, pathologic specimens from 77 patients with bladder TCC. These genes included basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), interleukin (IL)-8, matrix metalloproteinase (MMP)-9, and epidermal growth factor receptor (EGFR). Relative gene expression was quantified using image analysis. Gene expression was normalized using poly (dT) and the expression of each factor in a panel of specimens of normal urothelium. Patients were stratified according to disease stage, and the level of gene expression among the stratified groups was compared. VEGF, bFGF, IL-8, and MMP-9 expression was increased in muscle-invasive compared with superficial papillary tumors, (p<0.05) and VEGF expression was increased in muscle-invasive tumors compared with CIS specimens (p<0. 05). bFGF, IL-8, and EGFR expression was increased in CIS specimens compared with superficial papillary tumors (p<0.05). The pattern of expression of bFGF, VEGF, IL-8, MMP-9, and EGFR represent the divergent developmental pathways in the pathogenesis of bladder TCC, which characterizes superficial or invasive bladder cancer. bFGF, IL-8, and EGFR appear to be upregulated in early precursor lesions (CIS), whereas VEGF appears to be upregulated at later stages in the development of muscle-invasive TCC.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology
  • Colorimetry
  • Disease Progression
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / genetics
  • Gene Expression Regulation, Neoplastic*
  • Growth Substances / biosynthesis
  • Growth Substances / genetics
  • Humans
  • Image Processing, Computer-Assisted
  • In Situ Hybridization
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Lymphokines / biosynthesis
  • Lymphokines / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Receptors, Growth Factor / biosynthesis
  • Receptors, Growth Factor / genetics
  • Staining and Labeling
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Growth Substances
  • Interleukin-8
  • Lymphokines
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 9