DECREASED EXPRESSION OF KERATINOCYTE GROWTH-FACTOR RECEPTOR IN A SUBSET OF HUMAN TRANSITIONAL-CELL BLADDER CARCINOMAS

Growth factors and growth factor receptors are involved in tumor progr ession, The fibroblast growth factor receptor 2 gene encodes distinct isoforms, The isoforms which bind KGF (keratinocyte growth factor or F GF-7) are called KGF-R or FGFR2b. KGF-R is expressed in different epit helia and is involved in the control of epithelial-mesenchymal interac tions. Expression of KGF-R mRNA was examined in normal human bladder a nd transitional cell carcinoma of the bladder (TCC) by semi-quantitati ve RT-PCR using TFIID and GAPDH as internal standards, In normal bladd er, the KGF-R mRNA was detected in the urothelium but not in the under lying stroma, In TCCs, the level of KGF-R mRNA was generally either no rmal or low, Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal urothelium, This decrease in KGF-R mRNA was no t accompanied by an increase in BEK (FGFR2c) mRNA, the other major spl ice variant of the fibroblast growth factor receptor 2 gene, Expressio n of the KGF-R was also monitored by immunohistochemistry using a func tional KGF-immunoglobulin chimera, The receptor was uniformly expresse d throughout the normal urothelium except for the umbrella cells, Immu noreactivity for KGF-R was found to be negative in tumors with low lev els of KGF-R mRNA, while the peritumoral normal urothelium was positiv e, Among patients with muscle invasive tumors, those exhibiting a low level of HGF-R mRNA had a significantly higher proportion of cancer de aths, Our results suggest that decreased expression of KGF-R can be co nsidered as a marker of tumor progression in muscle invasive TCCs.