title: Prognostic implications of the expression of erbB2, topoisomerase II alpha and thymidylate synthase in metastatic gastric cancer after fluorouracil-based therapy.
abstract: 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).
  
  
  CONCLUSIONS
  High dose fluorouracil/leucovorin-based chemotherapy may have the potential to reverse the adverse effects resulting from erbB2 gene amplification in gastric cancer.
authors.affiliation: Division of Cancer Research, National Health Research Institutes, Veterans General Hospital, Shipai Rd, Sect 2, no. 201, Taipei, Taiwan. jmliu@nhri.org.tw
authors.forename: Jacqueline Ming
authors.initials: JM
authors.lastname: Liu
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Anna F Y
authors.initials: AF
authors.lastname: Li
authors.forename: Chew Wen
authors.initials: CW
authors.lastname: Wu
authors.forename: Chieh
authors.initials: C
authors.lastname: Lan
authors.forename: Tsai Rong
authors.initials: TR
authors.lastname: Chung
authors.forename: Her-Shyong
authors.initials: HS
authors.lastname: Shiah
authors.forename: Kuan Der
authors.initials: KD
authors.lastname: Lee
authors.forename: Tsang Wu
authors.initials: TW
authors.lastname: Liu
authors.forename: Jacqueline Whang
authors.initials: JW
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012186:Retroperitoneal Neoplasms / Q000556:secondary; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013940:Thymidylate Synthase / Q000096:biosynthesis*
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D005472:Fluorouracil; D002955:Leucovorin; D018719:Erb-b2 Receptor Tyrosine Kinases; D013940:Thymidylate Synthase