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

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