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

Objective: This retrospective study aimed to ascertain the expressionof erbB2 in relation to topoisomerase II (T2) and thymidylatesynthase (TS) markers in 30 consecutive metastatic gastric cancerpatients with a specimen available for study. Methods: All patients had been entered on consecutive chemotherapeuticclinical trials that were all 5-fluorouracil based. The specimenswere evaluated by fluorescence in situ hybridization to ascertainerbB2 and T2 gene amplification, and by immunohistochemicalstaining for T2 and TS protein expression. Results: erbB2 amplification was detected in 16.7% of specimens,with co-amplification of the T2 gene in 40%, and 44% had undetectableTS protein expression. Kaplan–Meier survival curves showedsignificantly prolonged overall survival in patients with erbB2and T2 gene amplification, T2 protein overexpression and absenceof TS protein expression (P = 0.0011, P = 0.0048, P = 0.0061and P = 0.0267, respectively, by log rank test). There was apositive correlation between erbB2 amplification and T2 amplification,T2 protein overexpression, and a trend towards absence of TSexpression (P = 0.0001, P = 0.003 and P = 0.066 by Fisher'sexact test). Conclusion: High dose fluorouracil/leucovorin-based chemotherapymay have the potential to reverse the adverse effects resultingfrom erbB2 gene amplification in gastric cancer.