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

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.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.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.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.