Prognostic Value of Expression of ERCC1, Thymidylate Synthase, and Glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin Chemotherapy in Advanced Gastric Cancer

Ann Oncol. 2007 Mar;18(3):504-9. doi: 10.1093/annonc/mdl430.

Abstract

Background: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy.

Patients and methods: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion at day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by 5-FU bolus 400 mg/m(2) and 22-h continuous infusion of 600 mg/m(2) at days 1-2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry.

Results: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037).

Conclusion: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • DNA-Binding Proteins / analysis*
  • Endonucleases / analysis*
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Glutathione S-Transferase pi / analysis*
  • Humans
  • Immunohistochemistry
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Thymidylate Synthase / analysis*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • Oxaliplatin
  • Thymidylate Synthase
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • ERCC1 protein, human
  • Endonucleases
  • Leucovorin
  • Fluorouracil