The expression of PAX5 in human transitional cell carcinoma of the bladder: relationship with de-differentiation

Objective To investigate the expression of PAX genes, a family of developme ntal control genes (which encode nine nuclear transcription factors essenti al for embryogenesis and are proto-oncogenes in mice) in human transitional cell carcinoma (TCC) of the bladder. Materials and methods PAX gene expression was assessed in three established bladder cancer cell lines and 29 primary tumours using the reverse transcr iptase-polymerase chain reaction and Southern analysis. Results All three established TCC cell lines and 79% of primary TCCs expres sed PAX5 mRNA. There was a significantly higher proportion of PAXS expressi on in malignant than in benign urothelium (P = 0.02, Fisher's exact test); nine of 12 pTa tumours (mucosa-confined), seven of eight pT1 (invading lami na propria) and eight of nine pT2 (invading muscle) expressed PAXS. A highe r proportion of tumours with increasing de-differentiation expressed PdX5, which correlates well with the expression pattern of PAXS in development. I n well-differentiated tumours (grade 1), half expressed PAXS, compared with 84% of moderately to poorly differentiated tumours (grades 2/3). The odds ratio for PAXS expression in malignancy suggests that it increases the risk of malignancy four-fold. Conclusion These data support a role for the PAX family in oncogenesis, by identifying another human neoplasm in which they are inappropriately expres sed. PAXS expression in undifferentiated TCC cells may contribute to pathog enesis by supporting cellular proliferation in the de-differentiated state, Furthermore, the high incidence of PAXS expression suggests its potential use as a diagnostic tool and therapeutic target in TCC.