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Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis

From the Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom.

Address reprint requests to Sanjay Popat, MD, Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK; e-mail: s.popat{at}icr.ac.uk

PURPOSE: A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients. Although most have reported poorer overall and progression-free survival with high TS expression, estimates of the hazard ratio (HR) between studies differ wildly. To derive a more precise estimate of the prognostic significance of TS expression, we have reviewed published studies and carried out a meta-analysis.

MATERIALS AND METHODS: Twenty studies stratifying overall survival and/or progression-free survival in CRC patients by TS expression status were eligible for analysis. The principal outcome measure was the HR. Data from these studies were pooled using standard meta-analysis techniques.

RESULTS: Thirteen studies investigated outcome in a total of 887 cases with advanced CRC, and seven studies investigated outcome in a total of 2,610 patients with localized CRC. A number of methods were used both to assess TS expression and to assign TS status. Sample sizes varied greatly, small sample sizes being a feature of the advanced disease studies. The combined HR estimate for overall survival (OS) was 1.74 (95% CI, 1.34 to 2.26) and 1.35 (95% CI, 1.07 to 1.80) in the advanced and adjuvant settings, respectively, but there was evidence of heterogeneity and possible publication bias.

CONCLUSION: Tumors expressing high levels of TS appeared to have a poorer OS compared with tumors expressing low levels. Additional studies with consistent methodology are needed to define the precise prognostic value of TS.

Supported by the United Kingdom Department of Health, the Alan Learner fund, and grants from Cancer Research UK and the Association for International Cancer Research.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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