Yonsei Med J.  2016 Jul;57(4):831-839. 10.3349/ymj.2016.57.4.831.

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

• Lim S
• Koh MJ
• Jeong HJ
• Cho NH
• Choi YD
• Cho DY
• Lee HY
• Rha SY

• KMID: 2374112
• DOI: http://doi.org/10.3349/ymj.2016.57.4.831

Abstract

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.

Keyword

Urinary bladder neoplasms; receptor tyrosine kinases; prognosis; cystectomy

MeSH Terms

Adult
Aged
Aged, 80 and over
Carcinoma/*metabolism/*mortality/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/*mortality/surgery
Urothelium/pathology
Receptor, ErbB-2
Receptor, Fibroblast Growth Factor, Type 1
Receptor, Fibroblast Growth Factor, Type 3

Figure

• 

  Fig. 1 Immunohistochemistry staining (×200) of urothelial carcinoma showing different grades of FGFR1 expression. (A) Negative. (B) Moderate signaling in 30% of cells. (C) Weak signaling in 70% of cells. (D) Moderate signaling in 70% of cells. FGFR1, fibroblast growth factor receptor 1.

• 

  Fig. 2 Distribution of patients according to the HER2 and FGFR expression status. HER2, human epidermal growth factor receptor 2; FGFR, fibroblast growth factor receptor.

• 

  Fig. 3 Survival curves according to FGFR1 expression level. (A) Progression free survival. (B) Overall survival. FGFR1, fibroblast growth factor receptor 1.

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