Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studies

Int J Cancer. 2008 Nov 15;123(10):2384-9. doi: 10.1002/ijc.23822.


The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine-based chemotherapy seemed inconclusive. To derive a more precise estimation of the relationship, a metaanalysis was performed. Studies have been identified by searching PubMed and Embase. Inclusion criteria were advanced CRC patients, received fluoropyrimidine-based chemotherapy and evaluation of TS expression and overall response rate (ORR). The relative ratio (RR) for ORR in patients with low-TS expression over those with high-TS expression with 95% confidence interval (CI) was calculated for each study as an estimation of the predictive effect of TS. A total of 24 studies including 1,112 patients were involved in this metaanalysis. The overall RR was 2.20 (95% CI, 1.82-2.66; p = 0.000). For studies evaluating TS expression in metastatic lesions, the pooled RR was 3.23 (95% CI, 2.27-4.59; p = 0.000); for studies testing TS expression in primary lesions, a pooled RR of 1.89 (95% CI, 1.45-2.48; p = 0.000) was estimated. Focusing the analysis on immunohistochemistry (IHC)-based or RTPCR-based assessments, the pooled RR was 1.83 (95% CI, 1.44-2.34; p = 0.000) and 2.96 (95% CI, 2.07-4.22; p = 0.000), respectively. The results indicated that low-TS expression tumors in advanced CRC patients were more sensitive to fluoropyrimidine-based chemotherapy. Subgroup analyses indicated that the predictive value of TS expression evaluated in metastases was more prominent than that of primary lesions, and that TS expression tested by RTPCR was also of greater predictive value than by IHC.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology*
  • Humans
  • Immunohistochemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Thymidylate Synthase / metabolism*


  • Antineoplastic Agents
  • Thymidylate Synthase