Tumor progression and chemosensitivity to uracil/tegafur in relation to the apoptosis related protens in gastric cancer

Abstract

4072 Background: Apoptosis related proteins including p53 and p21 regulate cell cycle under exposure of anticancer drugs. The Bax and Mcl-1 gene are members of the Bcl-2 family. Bcl-2 and Mcl-1 are blockers of cell death, whereas Bax and Bcl-Xs are promoters of apoptosis. Methods: To study apoptosis related protein expression and their impact on patient's survival time and chemosensitivity to postoperative UFT [uracil/tegafur 4:1], we examined mutant p53, p21, bax and Mcl-1 protein expression using immunohistochemical staining in 125 surgically resected gastric carcinomas invading the serosa (T3). Results: Expression of mutant p53, p21, Bax and Mcl-1 proteins were detected in 64%, 48%, 39% and 75% of patients, respectively. Mutant p53(+), p21(-) or Mcl-1(+) tumor was frequently observed in more advanced carcinomas. Patients with mutant p53(-), p21(+) or Mcl-1(-) tumor had better survival rates than those with mutant p53(+), p21(-) or Mcl-1(+) tumor, respectively. More p21(+) or Bax(+) cases and less mutant p53(+) or Mcl-1(+) cases were found in differentiated carcinoma. In patients with mutant p53(+), p21(+), Bax(-), or Mcl-1(-) tumor, no survival benefit was obtained by using UFT. In patients with mutant p53 tumor, however, 5-year survival rate of those given UFT was 72%, significantly superior to 35% of those not given the drug (P<0.05). In patients with p21(-) tumor, 54% of patients given UFT survived for 5 year, whereas all patients not given UFT died within 4 years (P<0.05). In patients with Bax(+) tumor, 5-year survival rates were 61% in those given UFT and 31% in those not given UFT (P<0.05). In patients with Mcl-1(+) tumor, 5-year survival rate of those given UFT was 57%, being significantly better than 32% of those not given the drug (P<0.01). Conclusions: These results indicate that the relationship of expression levels of p53, p21, Bax and Mcl-1 is important for predicting the efficacy of postoperative UFT. Therefore, patients with T3 gastric carcinoma should be selected for UFT treatment based on the expression of apoptosis related proteins in tumor cells. No significant financial relationships to disclose.