Fibroblast growth factors and their receptors in transitional cell carcinoma.
OBJECTIVE
The recent identification in transitional cell carcinoma of mutations in a fibroblast growth factor (FGF) receptor, namely FGF receptor-3, has provoked great interest in the potential usefulness of FGF receptors and their ligands as molecular markers and as targets for bladder cancer therapy. We examined these possibilities in light of the published literature.


METHODS
We reviewed the world literature on FGFs and their receptors from 1966 to January 2002 using PubMed.


RESULTS
The recent identification in transitional cell carcinoma of a high frequency of mutations in FGF receptor-3 predicted to activate kinase activity of the receptor indicate a likely role as an oncogene in the urothelium. The finding of FGF receptor-3 mutations only rarely in other tumor types to date indicates surprising urothelial specificity that requires tissue specific approaches for evaluation and exploitation. In contrast, FGF receptor-2 expression is down-regulated in bladder tumors, suggesting a possible tumor suppressor role. Information is available on the expression of FGF receptors-1 and 2 in normal bladder and urine, and in bladder tumors. These angiogenic factors represent potential urine markers of bladder neoplasia, although as single markers they lack sufficient sensitivity and specificity. Some interesting insights into the potential role of these factors have come from studies using in vitro model systems. However, there is little information on the numerous other members of this family of growth factors in the bladder and, therefore, much scope for future studies.


CONCLUSIONS
It is clear that the FGFs and their receptors have important roles in the development of transitional cell carcinoma. Undoubtedly it will be a focus for much future research. It can be anticipated that members of these protein families would represent useful clinical markers and potential targets for bladder cancer therapy.
Munro
Nicholas P
NP
Cancer Research United Kingdom Clinical Centre in Leeds, St James's University Hospital, Leeds, United Kingdom.
Knowles
Margaret A
MA
D000818:Animals; D015415:Biomarkers / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000652:urine; D006801:Humans; D009154:Mutation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D019459:Urothelium
D015415:Biomarkers; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors