- Research Article
7
- 10.1200/jco.2006.24.18_suppl.10011
Prognostic value of thymidylate synthase (TS) expression on failure-free survival of fluorouracil-treated metastatic colorectal cancer patients
- Jun 20, 2006
- Journal of Clinical Oncology
- S Richman + 9 more +9
10011 Background: We previously presented (ASCO 04 #9506) an exploratory analysis of 13 molecular markers in relation to clinical outcomes in 846 patients treated with fluorouracil (FU), or FU+irinotecan, or FU+oxaliplatin in a large UK-based randomized controlled trial (FOCUS - ASCO ’05 #3518). High TS IHC expression and tumor grade were highly significantly associated with reduced failure-free survival (FFS) in a multivariable model. We now present data from an independent validation set of 449 FOCUS patients and on the combined test and validation sets. Methods: Formalin-fixed, paraffin embedded blocks were retrieved from consenting patients and tissue microarrays made for IHC assessment. Factors assessed for the effect on FFS of first-line therapy were: liver metastases; ALP; grade; mucoid status; age; and IHC for dUTPase and TS. Log-rank univariate analyses and Cox Model multivariable analysis was performed. Results: Univariate analysis of the validation set failed to confirm evidence of the previously observed association between high TS expression and FFS (p=0.2); however high dUTPase IHC (p=0.01), ALP (p<0.0001) and grade (p=0.001) showed significant associations. Table 1 illustrates the results of univariate and multivariable analysis of the combined test and validation sets. In the Cox Model, high TS IHC expression, tumor grade and baseline serum ALP were highly significant predictors of reduced FFS. Conclusions: We failed to confirm a significant association between high TS expression and reduced FFS in an independent validation set. However, in an exploratory analysis of the combined validation and test sets (n>1000), TS IHC expression remained a highly significant predictor of FFS. Overall, our results cannot be taken to demonstrate a powerful and clinically useful influence of TS on treatment efficacy, but are consistent with a moderate effect. [Table: see text] No significant financial relationships to disclose.
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