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Predictive significance of thymidylate synthase and dihydropyrimidine dehydrogenase levels in patients with completely resected colorectal cancer receiving adjuvant 5-fluorouracil therapy



Predictive significance of thymidylate synthase and dihydropyrimidine dehydrogenase levels in patients with completely resected colorectal cancer receiving adjuvant 5-fluorouracil therapy



Journal of Clinical Oncology 23(16_Suppl): 3629-3629



NlmCategory="UNASSIGNED">3629 Background: Cytotoxic effect of 5-FU is mediated through competitive binding to thymidylate synthetase (TS), leading to thymine depletion. 5-FU is catabolized by dihydropyrimidine dehydrogenase (DPD). It is speculated that tumorcells with high levels of TS or DPD will be less sensitive to 5-FU therapy. The primary objective was to evaluate the predictive significance of TS and DPD levels in colorectal tumors on overall survival following complete resection and adjuvant 5-FU therapy. This is a retrospective study among consecutive patients completely resected for colorectal cancer stage III and treated with adjuvant 5-FU according to the Mayo-regimen. The intensity of TS and DPD were scored (0-3) using immunohistochemical staining Proportion of TS positive tumorcells were counted at the luminal surface of the tumor and at the border of tumor invasion of normal tissue, and analysed for the predictive significance to overall survival using Cox proportional hazard linear regression analysis. A total of 190 patients were included. Sixty patients have deceased during 9 years of follow up. In the multivariate analysis T-stage (p=0.001), N-stage (p=0.003) and performance status (p=0.02) were significant prognostic factors, while tumor site (p=0.28), age (p=0.36), intestinal perforation (p=0.23), perineural tumorcells (p=0.26), intravascular tumorcells (p=0.50), differentiation grade (p=0.35) and histologic type (p=0.44) were non significant. The intensity of TS (p=0.18) and proportion of TS positive tumorcells (p=0.25) at the site of tumor invasion of normal tissue were better predictors for survival than the intensity of TS (p=0.64) and proportion of TS positive tumorcells (p=0.96) at the luminal surface of the tumor. The DPD intensity of tumorcells turned out not to predict overall survival (p=0.68). Levels of TS and DPD enzymes in colorectal tumors were not predictive factors of overall survival of adjuvant 5-FU therapy in patients at high risk of recurrence of resected colon carcinoma. No significant financial relationships to disclose.

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Accession: 058597516

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PMID: 27944839


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