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

Francesca V. Negri, Cinzia Azzoni, Lorena Bottarelli, Nicoletta Campanini, Alessandra Mandolesi, Andrew Wotherspoon, David Cunningham, Mario Scartozzi, Stefano Cascinu, Carmine Tinelli, Enrico Maria Silini, Andrea Ardizzoni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4611-4617
Number of pages7
JournalAnticancer Research
Volume33
Issue number10
Publication statusPublished - Oct 2013

Keywords

  • 5-Fluorouracil
  • Microsatellite instability
  • Mucinous colorectal cancer
  • Thymidylate synthase
  • Topoisomerase-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Negri, F. V., Azzoni, C., Bottarelli, L., Campanini, N., Mandolesi, A., Wotherspoon, A., Cunningham, D., Scartozzi, M., Cascinu, S., Tinelli, C., Silini, E. M., & Ardizzoni, A. (2013). Thymidylate synthase, topoisomerase-1 and microsatellite instability: Relationship with outcome in mucinous colorectal cancer treated with fluorouracil. Anticancer Research, 33(10), 4611-4617.