Prognostic implications of the expression of erbB2, topoisomerase IIα and thymidylate synthase in metastatic gastric cancer after fluorouracil-based therapy

Objective: This retrospective study aimed to ascertain the expression of erbB2 in relation to topoisomerase IIα (T2α) and thymidylate synthase (TS) markers in 30 consecutive metastatic gastric cancer patients with a specimen available for study. Methods: All patients had been entered on consecutive chemotherapeutic clinical trials that were all 5-fluorouracil based. The specimens were evaluated by fluorescence in situ hybridization to ascertain erbB2 and T2α gene amplification, and by immunohistochemical staining for T2α and TS protein expression. Results: erbB2 amplification was detected in 16.7% of specimens, with co-amplification of the T2α gene in 40%, and 44% had undetectable TS protein expression. Kaplan-Meier survival curves showed significantly prolonged overall survival in patients with erbB2 and T2a gene amplification, T2α protein overexpression and absence of TS protein expression (P = 0.0011, P = 0.0048, P = 0.0061 and P = 0.0267, respectively, by log rank test). There was a positive correlation between erbB2 amplification and T2α amplification, T2α protein overexpression, and a trend towards absence of TS expression (P = 0.0001, P = 0.003 and P = 0.066 by Fisher's exact test). Conclusion: High dose fluorouracil/leucovorin-based chemotherapy may have the potential to reverse the adverse effects resulting from erbB2 gene amplification in gastric cancer.