OBJECTIVE: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides and as such a critical target for fluoropyrimidines, which are widely used in the treatment of colorectal cancer (CRC). The purpose of this study was to investigate TS expression in the primary tumours (PTs) and their metastases (M) in advanced CRC. MATERIAL AND METHODS: TS expression was determined immunohistochemically in paraffin-embedded biopsies of PT-M pairs in 39 CRC patients, as related to the clinical data. RESULTS: There was no difference in the mean TS index of PTs compared with that of M, 1.25 and 1.14, respectively (p=0.12). TS expression of PTs was above the mean more often than that of M (61.5% and 41.0%, respectively, p=0.035). High TS expression in PTs was significantly related to high expression in M (the Fisher exact test, p=0.001). Using the absolute index values, TS expression in PT and M was significantly correlated (Pearson R=0.501, p=0.001). In 29/39 (74.3%) pairs, PT and M had concordant expression levels (Cohen's kappa 0.508, 95% CI 0.260-0.756, p=0.001; intraclass correlation coefficient (ICC) = 0.679, 95% CI 0.358-0.836, p=0.0001). No significant association was found between TS expression and any of the clinicopathological variables, disease outcome (DFS, DSS) or its response to treatment in univariate or multivariate analysis. CONCLUSIONS: Albeit usually higher, TS expression in PT was closely correlated with TS expression in M. This suggests that measurement of TS in primary CRC accurately predicts TS expression in subsequent metastases, which may help in selecting those patients most likely to respond to 5-FU-based regimens.
Scand J Gastroenterol
471 - 476
Antimetabolites, Antineoplastic, Biomarkers, Tumor, Colorectal Neoplasms, Female, Fluorouracil, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Neoplasm Metastasis, Prognosis, Thymidylate Synthase