Prognostic Implications of the Expression of erbB2, Topoisomerase IIa 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 IIa (T2a) 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 T2a gene amplification, and by immunohistochemical staining for T2a and TS protein expression. Results: erbB2 amplification was detected in 16.7 % of specimens, with co-amplification of the T2a 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, T2a 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 T2a amplification, T2a 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. Key words: gastric cancer – erbB2 – topoisomerase IIa – survival – thymidylate synthas