High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy

Kun Huei Yeh, Chia Tung Shun, Chi Long Chen, Jaw Town Lin, Wei Jei Lee, Po Huang Lee, Yao Chang Chen, Ann Lii Cheng

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

BACKGROUND. In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS. To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS. Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P <0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P <0.01, log rank test). CONCLUSIONS. The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

Original languageEnglish
Pages (from-to)1626-1631
Number of pages6
JournalCancer
Volume82
Issue number9
DOIs
Publication statusPublished - May 1 1998
Externally publishedYes

Fingerprint

Thymidylate Synthase
Drug Resistance
Fluorouracil
Stomach
Carcinoma
Drug Therapy
Leucovorin
Gastrointestinal Agents
Chi-Square Distribution
Immunohistochemistry
Monoclonal Antibodies
Survival

Keywords

  • 5-Fluorouracil
  • Drug resistance
  • Gastric carcinoma
  • Thymidylate synthase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy. / Yeh, Kun Huei; Shun, Chia Tung; Chen, Chi Long; Lin, Jaw Town; Lee, Wei Jei; Lee, Po Huang; Chen, Yao Chang; Cheng, Ann Lii.

In: Cancer, Vol. 82, No. 9, 01.05.1998, p. 1626-1631.

Research output: Contribution to journalArticle

Yeh, Kun Huei ; Shun, Chia Tung ; Chen, Chi Long ; Lin, Jaw Town ; Lee, Wei Jei ; Lee, Po Huang ; Chen, Yao Chang ; Cheng, Ann Lii. / High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy. In: Cancer. 1998 ; Vol. 82, No. 9. pp. 1626-1631.
@article{f7502eb5e01945e3817a2e2d6eebd773,
title = "High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy",
abstract = "BACKGROUND. In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS. To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS. Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3{\%}) and 14 (46.7{\%}) had high and low expression of TS, respectively. Two of the 16 patients (12.5{\%}) with high expression of TS and 13 of the 14 patients (92.9{\%}) with low expression of TS responded to chemotherapy (P <0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P <0.01, log rank test). CONCLUSIONS. The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.",
keywords = "5-Fluorouracil, Drug resistance, Gastric carcinoma, Thymidylate synthase",
author = "Yeh, {Kun Huei} and Shun, {Chia Tung} and Chen, {Chi Long} and Lin, {Jaw Town} and Lee, {Wei Jei} and Lee, {Po Huang} and Chen, {Yao Chang} and Cheng, {Ann Lii}",
year = "1998",
month = "5",
day = "1",
doi = "10.1002/(SICI)1097-0142(19980501)82:9<1626::AID-CNCR5>3.0.CO;2-8",
language = "English",
volume = "82",
pages = "1626--1631",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy

AU - Yeh, Kun Huei

AU - Shun, Chia Tung

AU - Chen, Chi Long

AU - Lin, Jaw Town

AU - Lee, Wei Jei

AU - Lee, Po Huang

AU - Chen, Yao Chang

AU - Cheng, Ann Lii

PY - 1998/5/1

Y1 - 1998/5/1

N2 - BACKGROUND. In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS. To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS. Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P <0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P <0.01, log rank test). CONCLUSIONS. The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

AB - BACKGROUND. In the past 4 years, the weekly 24-hour infusion of high dose 5-fluorouracil (5-FU) and leucovorin in the treatment of patients with advanced gastric carcinoma has been prospectively studied at the authors' institution. This has enabled them to explore the possibility that the level of expression of thymidylate synthase (TS), the target enzyme of 5-FU, is related to the drug sensitivity of gastric carcinoma to 5-FU-based chemotherapy. METHODS. To be eligible for this study, patients were required to have received high dose 5-FU and leucovorin chemotherapy (weekly 24-hour infusions of 5-FU, 2,600 mg/m2, and leucovorin, 300 mg/m2) and to have had adequate prechemotherapy gastric carcinoma tissues for immunohistochemical study. TS106 monoclonal antibody was used to detect the expression of TS. A visual scoring system, which ranged from 0 to 3+, was adopted by 2 independent pathologists to semiquantitate the intensity of TS expression. RESULTS. Between 1993 and 1996, a total of 30 patients, 18 men and 12 women, with a median age of 61.5 years, were enrolled. Of these patients, 16 (53.3%) and 14 (46.7%) had high and low expression of TS, respectively. Two of the 16 patients (12.5%) with high expression of TS and 13 of the 14 patients (92.9%) with low expression of TS responded to chemotherapy (P <0.001, chi-square test). The median overall survival was 10 months for patients with low TS expression and 4 months for patients with high TS expression (P <0.01, log rank test). CONCLUSIONS. The data from this study suggest that the expression of TS, as determined by immunohistochemistry, is a relatively reliable indicator of whether 5-FU should be used in the treatment of patients with gastric carcinoma.

KW - 5-Fluorouracil

KW - Drug resistance

KW - Gastric carcinoma

KW - Thymidylate synthase

UR - http://www.scopus.com/inward/record.url?scp=0032080712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032080712&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(19980501)82:9<1626::AID-CNCR5>3.0.CO;2-8

DO - 10.1002/(SICI)1097-0142(19980501)82:9<1626::AID-CNCR5>3.0.CO;2-8

M3 - Article

C2 - 9576280

AN - SCOPUS:0032080712

VL - 82

SP - 1626

EP - 1631

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 9

ER -