Immunohistochemical Evaluation of Thymidylate Synthase in Gastric Carcinoma Using a New Polyclonal Antibody: The Clinical Role of Thymidylate Synthase as a Prognostic Indicator and Its Therapeutic Usefulness

Cancer. 1998 Oct 1;83(7):1300-6. doi: 10.1002/(sici)1097-0142(19981001)83:7<1300::aid-cncr5>;2-m.


Background: Before this study was conducted, the clinical and therapeutic significance of immunohistochemical evaluation of thymidylate synthase (TS) in patients with gastric carcinoma had not yet been clarified.

Methods: TS was immunohistochemically evaluated in 134 gastric carcinomas using anti-TS antibody. TS expression, 11 clinicopathologic variables, and survival were studied, and the correlations among them were investigated.

Results: The groups with high and low TS levels consisted of 56 and 78 patients, respectively. Granular cytoplasmic staining patterns of tumor cells were produced by immunohistochemical staining of the gastric carcinoma tissues. The grade of TS staining was significantly correlated with three clinicopathologic variables: depth of invasion, peritoneal metastasis, and stage of the carcinoma (P < 0.05). A univariate analysis revealed that the 5-year survival was significantly better for the low TS group than for the high TS group (P < 0.05): 65.2% for the low TS group and 43.2% for the high TS group. The group with high grade TS staining who received chemotherapy because of the advanced stage of their disease had worse prognoses even if they received adjuvant chemotherapy. A multivariate analysis revealed that four variables (peritoneal metastasis, lymphatic invasion, liver metastasis, and TS staining grade) independently contributed to survival (P < 0.05). The hazard ratio for the group with low grade TS staining was 0.464 compared with the group with high grade staining.

Conclusions: The immunohistochemical evaluation of TS using this anti-TS antibody may be clinically and therapeutically useful in determining the prognosis of gastric carcinoma patients.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies
  • Antimetabolites, Antineoplastic / therapeutic use
  • Carcinoma, Signet Ring Cell / drug therapy
  • Carcinoma, Signet Ring Cell / enzymology*
  • Carcinoma, Signet Ring Cell / mortality
  • Carcinoma, Signet Ring Cell / pathology
  • Drug Resistance
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Thymidylate Synthase / analysis*
  • Thymidylate Synthase / immunology


  • Antibodies
  • Antimetabolites, Antineoplastic
  • Thymidylate Synthase
  • Fluorouracil