Expression of thymidylate synthase in primary colorectal carcinoma and their corresponding metastases

Abstract

13587 Objective: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides required for DNA synthesis and is a critical target for fluoropyrimidines, which are widely used in the treatment of gastrointestinal tumours. Tumour TS expression was analysed in a series of 39 patients diagnosed and treated for Duke’s B, C and D colorectal cancer between January 1996 and August 2003 to investigate the role of TS in the development of metastatic phenotype in CRC. Methods: TS expression was determined immunohistochemically in 39 paraffin-embedded primary and metastatic tumour sections and the overall staining index was calculated according to the intensity of the cytoplasmic staining (0, 1, 2, 3) and the fraction of the corresponding tumour cells in the sample. Results: Tumours were classified as showing either lower or higher TS expression, i.e. below- or above the mean. In 29/39 (74.3%) pairs, the primary tumours and their metastases are concordant. In 10 out of 39 (25.7%) discordant pairs, TS expression was high in the primary tumours and low in the metastasis in 9/10 cases, and opposite in the remaining one case. Using the absolute staining index values, TS expression in the primary tumours and in the metastases was also significantly correlated (Pearson R=0.501, p=0.001). Conclusion: Between the paired primary tumours and distant metastatic lesion, the TS expression is in the majority higher in primary tumours compared to the metastasis and more concordant cases showed compared to discordant cases and in 9/10 discordant cases, TS expression in the primary tumours was above the mean and below the mean in their corresponding metastases compare to only one case showing the opposite pattern. No significant financial relationships to disclose.