BCL-2 BAX EXPRESSION AND P53 GENE STATUS IN HUMAN BLADDER-CANCER - RELATIONSHIP TO EARLY RECURRENCE WITH INTRAVESICAL CHEMOTHERAPY AFTER RESECTION/

Purpose: Studies have shown that the effects of chemotherapy depend on some biochemical mechanisms to induce apoptosis. Many genes are invol ved in apoptosis modulation, including p53, bcl-2 and bar. We determin ed the roles of p53 status and the ratio of bcl-2/bax proteins for pre dicting the recurrence of bladder superficial transitional cell carcin oma that had been treated with intravesical chemotherapy after resecti on. Materials and Methods: We performed Western blot analysis to expre ss bcl-2 and bar proteins, and PCR-SSCP to determine the alteration in the p53 gene in 43 patients with transitional cell carcinoma of the b ladder treated with intravesical chemotherapy after tumor resection. R esults: The expression of bcl-2 or bar did not correlate with histolog ical grade, clinical stage or relapse. In cases of relapse within 1 ye ar after resection bcl-2/bax was greater than and less than 1 in 50 an d 11%, respectively (p <0.01). Recurrence within 1 year after the init ial operation was also more common in patients with than without p53 g ene mutation (64 versus 22%, p <0.05). Furthermore, bcl-2/bax greater than and less than 1 was associated with p53 gene mutation in 38 and 1 1% of cases, respectively (p <0.05). Conclusions: A bcl-2/bax ratio gr eater than 1 and p53 gene mutation were closely associated with early relapse in patients with superficial transitional cell carcinoma of th e bladder during intravesical chemotherapy after resection. This findi ng suggests that the relative levels of bcl-2 and bar, and p53 gene st atus may contribute to drug sensitivity and progression, and help to p redict recurrence. Moreover, bcl-2/bax correlated with p53 status, whi ch implies that cross talk among bcl-2, bar and p53 has a role in infl uencing drug induced apoptosis and regulating resistance to chemothera py.