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Japanese Journal of Clinical Oncology 2004 34(12):727-732; doi:10.1093/jjco/hyh137
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© 2004 Foundation for Promotion of Cancer Research

Prognostic Implications of the Expression of erbB2, Topoisomerase II{alpha} and Thymidylate Synthase in Metastatic Gastric Cancer After Fluorouracil-based Therapy

Jacqueline Ming Liu1, Li-Tzong Chen1,5, Anna F. Y. Li2,4, Chew Wen Wu3,4, Chieh Lan1, Tsai Rong Chung1, Her-Shyong Shiah1, Kuan Der Lee1, Tsang Wu Liu1 and Jacqueline Whang Peng1

1 Division of Cancer Research, National Health Research Institutes, 2 Pathology Department and 3 Surgery Department, Veterans General Hospital-Taipei, 4 National Yang Ming University Medical School and 5 Department of Internal Medicine, Kaohsiung Medical University Hospital, Taipei, Taiwan

For reprints and all correspondence: Jacqueline M. Liu, Division of Cancer Research, National Health Research Institutes, c/o A191 Taipei-Veterans General Hospital, Shipai Rd, Sect 2, no. 201, Taipei, Taiwan. E-mail: jmliu{at}nhri.org.tw

Received July 1, 2004; accepted October 9, 2004

Objective: This retrospective study aimed to ascertain the expression of erbB2 in relation to topoisomerase II{alpha} (T2{alpha}) 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 T2{alpha} gene amplification, and by immunohistochemical staining for T2{alpha} and TS protein expression.

Results: erbB2 amplification was detected in 16.7% of specimens, with co-amplification of the T2{alpha} gene in 40%, and 44% had undetectable TS protein expression. Kaplan–Meier survival curves showed significantly prolonged overall survival in patients with erbB2 and T2{alpha} gene amplification, T2{alpha} 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 T2{alpha} amplification, T2{alpha} 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 II{alpha} • survival • thymidylate synthase


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