Differential expression of progression-related genes in the evolution of superficial to invasive transitional cell carcinoma of the bladder

It is generally accepted that there are dichotomous biologic pathways that lead to the development of either: i) superficial papillary (Ta) transition al cell carcinoma (TCC) or ii) precursor lesions to muscle-invasive (CIS, T 1) TCC and muscle-invasive (greater than or equal to T2) TCC. We investigat ed the expression of several progression-related genes to characterize the phenotype of these tumors within these divergent developmental pathways. Us ing a colorimetric in situ hybridization technique, we examined the express ion of mRNAs of several progression-related genes in archival, pathologic s pecimens from 77 patients with bladder TCC. These genes included basic fibr oblast growth factor (bFGF), vascular endothelial growth factor (VEGF), int erleukin (IL)-8, matrix metalloproteinase (MMP)-9, and epidermal growth fac tor receptor (EGFR). Relative gene expression was quantified using image an alysis. Gene expression was normalized using poly (dT) and the expression o f each factor in a panel of specimens of normal urothelium. Patients were s tratified according to disease stage, and the level of gene expression amon g the stratified groups was compared. VEGF, bFGF, IL-8, and MMP-9 expressio n was increased in muscle-invasive compared with superficial papillary tumo rs, (p<0.05) and VEGF expression was increased in muscle-invasive tumors co mpared with CIS specimens (p<0.05). bFGF, IL-8, and EGFR expression was inc reased in CTS specimens compared with superficial papillary tumors (p<0.05) . The pattern of expression of bFGF, VEGF, IL-8, MMP-9, and EGFR represent the divergent developmental pathways in the pathogenesis of bladder TCC, wh ich characterizes superficial or invasive bladder cancer. bFGF, IL-8, and E GFR appear to be upregulated in early precursor lesions (CIS), whereas VEGF appears to be upregulated at later stages in the development of muscle-inv asive TCC.