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

BACKGROUND. Before this study was conducted, the clinical and therapeu tic significance of immunohistochemical evaluation of thymidylate synt hase (TS) in patients with gastric carcinoma had not yet been clarifie d. METHODS. TS was immunohistochemically evaluated in 134 gastric carc inomas using anti-TS antibody. TS expression, 11 clinicopathologic var iables, and survival were studied, and the correlations among them wer e investigated. RESULTS. The groups with high and low TS levels consis ted 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 signif icantly correlated with three clinicopathologic variables: depth of in vasion, peritoneal metastasis, and stage of the carcinoma (P < 0.05). A univariate analysis revealed that the 5-year survival was significan tly 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 recei ved 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 0.4 64 compared with the group with high grade staining. CONCLUSIONS. The immunohistochemical evaluation of TS using this anti-TS antibody may b e clinically and therapeutically useful in determining the prognosis o f gastric carcinoma patients. Cancer 1998;83:1300-6. (C) 1998 American Cancer Society.