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 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.
Liu
Jacqueline Ming
JM
Division of Cancer Research, National Health Research Institutes, Veterans General Hospital, Shipai Rd, Sect 2, no. 201, Taipei, Taiwan. jmliu@nhri.org.tw
Chen
Li-Tzong
LT
Li
Anna F Y
AF
Wu
Chew Wen
CW
Lan
Chieh
C
Chung
Tsai Rong
TR
Shiah
Her-Shyong
HS
Lee
Kuan Der
KD
Liu
Tsang Wu
TW
Peng
Jacqueline Whang
JW
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*
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