FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 6; pp. 1911 - 1914
• Main Authors: VAN RHIJN, Bas W. G, VAN DER KWAST, Theo H, VIS, André N, KIRKELS, Wim J, BOEVE, Egbert R, JÖBSIS, Adriaan C, ZWARTHOFF, Ellen C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-03-2004
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Female; Genes, p53 - genetics; Humans; Male; Medical sciences; Mutation; Neoplasm Staging; Pharmacology. Drug treatments; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor - genetics; Signal Transduction - genetics; Survival Rate; Tumors; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urothelium - pathology; Signal transduction; Carcinoma; TP53 Gene; Pathogenesis; Genetics; Malignant tumor; Tumor suppressor gene; Fibroblast growth factor receptor 3
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-03-2421

Fibroblast growth factor receptor 3 (FGFR3) and P53 mutations are frequently observed in bladder cancer. We here describe the distribution of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell carcinomas. FGFR3 mutations were observed in 59% and P53 overexpression in 25%. Interestingly, FGFR3 and P53 alterations were mutually exclusive, because they coincided in only 5.7% of tumors. Consequently, we propose that they characterize two alternative genetic pathways in urothelial cell carcinoma pathogenesis. The genetic alterations were reflected in the pathology and the clinical outcome, i.e., FGFR3 mutations were found in low-stage/-grade tumors and were associated with a favorable disease course, whereas P53 alterations were tied to adverse disease parameters.