Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer.

PURPOSE

We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy.

METHODS

We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test.

RESULTS

Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors.

CONCLUSIONS

The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.