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Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection

  1. Kimberly M. Rieger-Christ Ph.D.1,†,
  2. Arthur Mourtzinos M.D.2,†,‡,
  3. Peter J. Lee M.D.2,
  4. Ralph M. Zagha M.D.2,
  5. Jason Cain B.S.1,
  6. Mark Silverman M.D.3,
  7. John A. Libertino M.D.2,
  8. Ian C. Summerhayes Ph.D.1,§,*

Article first published online: 25 JUN 2003

DOI: 10.1002/cncr.11536

Issue

Cancer

Cancer

Volume 98, Issue 4, pages 737–744, 15 August 2003

Additional Information

How to Cite

Rieger-Christ, K. M., Mourtzinos, A., Lee, P. J., Zagha, R. M., Cain, J., Silverman, M., Libertino, J. A. and Summerhayes, I. C. (2003), Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection. Cancer, 98: 737–744. doi: 10.1002/cncr.11536

Author Information

  1. 1

    Cell and Molecular Biology Laboratory, Robert E. Wise M. D. Research and Education Institute, Burlington, Massachusetts

  2. 2

    Department of Urology, Lahey Clinic, Burlington, Massachusetts

  3. 3

    Department of Pathology, Lahey Clinic, Burlington, Massachusetts

  1. †

    Dr. Rieger-Christ and Dr. Mourtzinos were equal contributors to this work.

  2. ‡

    Dr. Arthur Mourtzinos is a Robert E. Wise Research Fellow.

  3. §

    Fax: (781) 744-2984

*Cell and Molecular Biology Laboratory, Robert E. Wise M. D. Research and Education Institute, Lahey Clinic, 31 Mall Road, Burlington, MA 01805

Publication History

  1. Issue published online: 1 AUG 2003
  2. Article first published online: 25 JUN 2003
  3. Manuscript Accepted: 22 APR 2003
  4. Manuscript Revised: 18 APR 2003
  5. Manuscript Received: 6 FEB 2003

Funded by

  • NIH Grant. Grant Number: R01-DK59400

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Keywords:

  • bladder;
  • urine sediment DNA;
  • FGFR3;
  • single-strand conformation polymorphism;
  • mutation

Abstract

BACKGROUND

Mutations in fibroblast growth factor 3 receptor (FGFR3) are frequent events in low-grade bladder tumors. To assess the potential utility of the detection of FGFR3 mutations in a screening modality, the authors analyzed urine sediment DNA samples from 192 patients in a retrospective study.

METHODS

Urine sediment DNA samples from 192 patients were prepared. Seventy-two patients had undergone transurethral resection (TURBT group) of mainly Ta lesions and 120 patients had undergone cystectomy (cystectomy group). The majority of patients in the cystectomy group had more advanced tumors compared with patients in the TURBT group. DNA preparations were screened for FGFR3 mutations in exons 7, 10, and 15 using single-strand conformation polymorphism (SSCP) and DNA sequencing.

RESULTS

Using SSCP, 67% of patients in the TURBT group and 28% in the cystectomy group displayed FGFR3 mutations. Comparative analysis of cytology results and FGFR3 mutational analysis were performed in 122 cases. Within the TURBT group, FGFR3 mutation analysis outperformed cytology. FGFR3 mutation analysis identified change in 68% of urine sediment DNA samples whereas cytology recorded the presence of tumor cells in 32% of the DNA samples. In the cystectomy group, cytology outperformed FGFR3 mutation analysis. Cytology recorded tumor detection in 90% of patients, while SSCP identified mutational change in 24%.

CONCLUSIONS

Combining FGFR3 mutation results with cytology in both groups correctly identified tumor presence in 105 of 122 (86%) of patients. The greater sensitivity of FGFR3 mutation detection over cytology in identifying the presence of low-grade, superficial bladder tumors represents a potential new tool to complement standard cytology in screening patients for bladder tumors and recurrent disease. Cancer 2003;98:737–44. © 2003 American Cancer Society.

DOI 10.1002/cncr.11536

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