Thymidylate synthase, topoisomerase-1 and microsatellite instability: relationship with outcome in mucinous colorectal cancer treated with fluorouracil

Anticancer Res. 2013 Oct;33(10):4611-7.

Abstract

Background: Mucinous colorectal cancer (CRC) exhibits distinct clinical and pathological features, including poorer response to fluorouracil (FU) compared with non-mucinous tumours.

Patients and methods: We compared the expression of thymidylate synthase (TYMS) and topoisomerase-1 (TOPO1) and DNA microsatellite instability (MSI) in 87 patients (35 mucinous and 52 non-mucinous CRCs) enrolled in three randomized trials, evaluating infused FU as first-line treatment.

Results: Mucinous CRCs more frequently had high TOPO1 expression than did non-mucinous tumors (41% vs. 15%, p=0.028). The median overall survival was 14.2 months for patients with mucinous CRC with low TOPO1 expression compared with 9.7 months for high TOPO1-expressing cases (p=0.016). After adjusting for confounding variables, low TOPO1 expression was statistically favourably associated with overall survival (hazard ratio=0.55; p=0.041).

Conclusion: Our data suggest the TOPO1 expression levels to be a prognostic marker in patients with mucinous CRC treated with FU. If further verified, these data might redefine therapeutic strategies by identifying categories of patients with a worse prognosis.

Keywords: 5-fluorouracil; Mucinous colorectal cancer; microsatellite instability; thymidylate synthase; topoisomerase-1.

MeSH terms

  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / enzymology*
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / secondary
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Topoisomerases, Type I / metabolism*
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use*
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Thymidylate Synthase / metabolism*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Thymidylate Synthase
  • DNA Topoisomerases, Type I
  • TOP1 protein, human
  • Fluorouracil