Bcl-2/bax EXPRESSION AND p53 GENE STATUS IN HUMAN BLADDER CANCER: RELATIONSHIP TO EARLY RECURRENCE WITH INTRAVESICAL CHEMOTHERAPY AFTER RESECTION

Abstract

Purpose Studies have shown that the effects of chemotherapy depend on some biochemical mechanisms to induce apoptosis. Many genes are involved in apoptosis modulation, including p53, bcl-2 and bax. We determined the roles of p53 status and the ratio of bcl-2/bax proteins for predicting the recurrence of bladder superficial transitional cell carcinoma that had been treated with intravesical chemotherapy after resection. Materials and Methods We performed Western blot analysis to express bcl-2 and bax proteins, and PCR-SSCP to determine the alteration in the p53 gene in 43 patients with transitional cell carcinoma of the bladder treated with intravesical chemotherapy after tumor resection. Results The expression of bcl-2 or bax did not correlate with histological grade, clinical stage or relapse. In cases of relapse within 1 year after resection bcl-2/bax was greater than and less than 1 in 50 and 11%, respectively (p <0.01). Recurrence within 1 year after the initial operation was also more common in patients with than without p53 gene 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 11% of cases, respectively (p <0.05). Conclusions A bcl-2/bax ratio greater than 1 and p53 gene mutation were closely associated with early relapse in patients with superficial transitional cell carcinoma of the bladder during intravesical chemotherapy after resection. This finding suggests that the relative levels of bcl-2 and bax, and p53 gene status may contribute to drug sensitivity and progression, and help to predict recurrence. Moreover, bcl-2/bax correlated with p53 status, which implies that cross talk among bcl-2, bax and p53 has a role in influencing drug induced apoptosis and regulating resistance to chemotherapy.