DBC1 and FGFR3 expression as indicators of tumor progression and recurrence in superficial bladder cancer
U.Sommer1, M.I.Toma1, M.O.Grimm², S. Füssel², M.P. Wirth², G.B. Baretton1
1 Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, Dresden
2 Klinik und Poliklinik für Urologie, Universitätsklinikum Carl Gustav Carus, Dresden
Aims: This study explores the expression of DBC1 (deleted in bladder cancer locus 1, a candidate tumor suppressor gene on 9p32-33) and FGFR3 in superficial and invasive bladder cancer (BCa) and the correlation to recurrence and progress.
Methods: Tissue microarrays (TMA) from archival material from 117 patients undergoing transurethral resection (TUR) or cystoprostatectomy for superficial BCa were included in the study. 55 patients showed no recurrence or progression after TUR, 45 patients showed recurrence after first therapy and 17 patients showed disease progression. The immunohistochemistry for DBC1 was done with a polyclonal antibody (Protein Tech Group). For FGFR3 we used a mouse monoclonal antibody (Santa Cruz Biotech). Primary antibody incubation was followed by detection with EnVision Plus (Dako, Denmark). For DBC1, cytoplasmic expression was evaluated and the cases were separated in positive and negative; for FGFR3 cytoplasmic and nuclear expression was studied and separated in negative, weak, moderate or strong. Statistical analysis was done by SPSS 17 for Windows.
Results: Normal urothelium is always positive for DBC1 and FGFR3. A statistically significant loss of DBC1 expression was observed in progressive and recurrent BCa compared with cases without recurrence (p<0.05). G2 tumors showed statistically significant loss of DBC1 compared with G1 and G3 tumors (p<0.001). Also significant differences in DBC1 expression were noticed in pTa tumors compared with pT1 tumors (p=0.002). Significant differences in FGFR3 expression was noticed also in cases with progression and recurrence compared with cases without progression or recurrence (p<0.05). The FGFR3 expression is different in normal urothelium, pTa and pT1 cases, respectively. Also significant differences were found in BCa depending on differentiation (p<0.02). No correlation to overall or tumor specific survival was noticed for DBC1 or FGFR3 expression.
Conclusions: Loss of DBC1 is correlated with increased tumor stage in BCa. The FGFR3 expression is significantly correlated with tumor stage and grade in BCa. FGFR3 expression and loss of DBC1 could be indicators for tumor progression or recurrence in superficial BCa.