Thymidylate Synthase Expression in Normal Colonic Mucosa: A Predictive Marker of Toxicity in Colorectal Cancer Patients Receiving 5-Fluorouracil-Based Adjuvant Chemotherapy

Abstract

Objectives: We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy. Methods: TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes’ stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy. Results: The incidence of grade 2–3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation. Conclusions: Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities.