Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma

Yonsei Med J. 2016 Jul;57(4):831-9. doi: 10.3349/ymj.2016.57.4.831.


Purpose: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients.

Materials and methods: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3).

Results: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis.

Conclusion: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.

Keywords: Urinary bladder neoplasms; cystectomy; prognosis; receptor tyrosine kinases.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / metabolism*
  • Carcinoma / mortality*
  • Carcinoma / surgery
  • Cystectomy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Muscles / pathology
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Retrospective Studies
  • Survival Rate
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / surgery
  • Urothelium / pathology


  • ERBB2 protein, human
  • FGFR1 protein, human
  • FGFR3 protein, human
  • Receptor, ErbB-2
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 3