Moleculair graderen van urotheelcelcarcinoom met FGFR3 en MIB-1: Reproduceerbaarder en beter dan klassieke pathologie t.a.v. klinische prognose

Translated title of the contribution: Molecular grading of urothelial cell carcinoma with FGFR3 and MIB-1 is superior to pathological grade for the prediction of clinical outcome

Bas W.G. Van Rhijn, André N. Vis, Theo H. Van Der Kwast, Wim J. Kirkels, François Radvanyi, Engelbert C.M. Ooms, Dominique K. Chopin, Egbert R. Boevé, Adriaan C. Jöbsis, Ellen C. Zwarthoff

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Fibroblast growth factor receptor 3 (FGFR3) mutations were recently found at a high frequency in well-differentiated urothelial cell carcinoma (UCC). We investigated the relationship between FGFR3 status and three molecular markers (MIB-1, P53 and P27kip1) associated with worse prognosis and determined the reproducibility of pathological grade and molecular variables. In this multi-center study, we included 286 patients with primary (first diagnosis) UCC. The histological slides were reviewed. FGFR3 status was examined by PCR-SSCP and sequencing. Expression levels of MIB-1, P53 and P27kip1 were determined by immunohistochemistry. Mean follow-up was 5.5 years (range, 0.4-18.4 years). FGFR3 mutations were detected in 172/286 (60%) of UCCs. G1-tumors had a FGFR3 mutation in 88% of cases, G3-tumors in 16%. Conversely, aberrant expression patterns of MIB-1, P53 and P27kip1 were seen in 5%, 2% and 3% of G1-tumors and in 85%, 60% and 56% of G3-tumors, respectively. In multivariate analysis with recurrence rate, progression and disease specific survival as endpoints, the combination of FGFR3 and MIB-1 proved of independent significance in all three cases. Using these two molecular markers, three molecular grades (mG) could be identified: mG1 (mutation; normal expression), favorable prognosis; mG2 (two remaining combinations), intermediate prognosis; mG3 (no mutation; high expression), poor prognosis. The molecular variables were more reproducible than pathological grade (85-100% vs. 47-61%). The FGFR3 mutation represents the favorable molecular pathway of UCC. Molecular grading provides a new, simple and highly reproducible tool for clinical decision making in UCC patients.

Translated title of the contributionMolecular grading of urothelial cell carcinoma with FGFR3 and MIB-1 is superior to pathological grade for the prediction of clinical outcome
Original languageDutch
Pages (from-to)35-46
Number of pages12
JournalNederlands Tijdschrift voor Urologie
Volume12
Issue number2
Publication statusPublished - Apr 2004

Keywords

  • FGFR3
  • MIB-1
  • Mutation
  • P27
  • P53
  • Urothelial cancer

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