TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND AND OBJECTIVES: Distant metastatic relapse occurs in approximately 20% of rectal cancer patients treated with 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by surgery. This study aimed to investigate mRNA level of 5-FU metabolizing enzymes in post-treatment specimens and to evaluate their predictive value of distant recurrence after CRT.
METHODS: Forty patients with rectal cancer underwent 5-FU-based CRT followed by surgery. After microdissection, total RNA of residual cancer was isolated from formalin-fixed paraffin-embedded (FFPE) specimens. Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) as 5-FU metabolizing enzyme were measured using real-time reverse transcription polymerase chain reaction.
RESULTS: Patients (n = 6) who developed distant recurrence had a significantly higher TS (P = 0.01), DPD (P = 0.02), and TP (P = 0.01) levels, compared with those patients (n = 34) without recurrence. High TS, DPD, and positive lymph node metastasis (pN) were significantly poorer prognostic factors for DFS (TS: P < 0.01, DPD: P < 0.01, pN: P < 0.05).
CONCLUSIONS: High TS and DPD mRNA levels on FFPE specimens may predict distant recurrence of rectal cancer treated with 5-FU-based preoperative CRT followed by surgery. Expression analysis of 5-FU metabolizing enzyme in residual cancer may be useful for treatment stratification and clinical management in these patients.