title: TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy.
abstract: OBJECTIVE
  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.
authors: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Mie, Japan. qouji@clin.medic.mie-u.ac.jp
authors: Koji
authors: K
authors: Tanaka
authors: Susumu
authors: S
authors: Saigusa
authors: Yuji
authors: Y
authors: Toiyama
authors: Yuki
authors: Y
authors: Koike
authors: Yoshinaga
authors: Y
authors: Okugawa
authors: Takeshi
authors: T
authors: Yokoe
authors: Yasuhiro
authors: Y
authors: Inoue
authors: Minako
authors: M
authors: Kobayashi
authors: Chikao
authors: C
authors: Miki
authors: Masato
authors: M
authors: Kusunoki
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D059248:Chemoradiotherapy; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D016612:Paraffin Embedding; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil