title: Comparative analysis of thymidylate synthase at the protein, mRNA, and DNA levels as prognostic markers in colorectal adenocarcinoma.
abstract: OBJECTIVE
  To determine the best routinely available molecular methodology for assessing thymidylate synthase (TS) as a prognostic marker in colorectal adenocarcinoma, TS was examined at the protein, mRNA, and DNA levels. Direct comparison of these routinely available assays has not been systematically studied across a large colon cancer patient cohort with long-term follow-up.
  
  
  METHODS
  We studied 150 surgically resected colorectal adenocarcinoma patients who received postoperative 5-Fluorouracil (5-FU) chemotherapy. TS immuunohistochemistry and real-time quantitative RT-PCR and PCR genotyping on patient-matched tumor and normal tissues were performed.
  
  
  RESULTS
  Surprisingly, mRNA values in normal tissue varied from 0.11 to 62.0 and significantly correlated with mRNA values of matched tumor tissues. Although higher tumor/normal ratios of mRNA expression trended toward poorer patient survival, neither this nor TS immunohistochemistry results were statistically significant predictors. TS tumor genotype was generally concordant with matched normal tissues. Further, the 2R/3R genotype of 5'-TSER was significantly correlated with poorer patient survival (P = 0.0249) and was also an independent prognostic marker on multivariate analysis.
  
  
  CONCLUSIONS
  TS genotyping on paraffin-embedded fixed tissues proved to be the most useful method for prediction of outcome of 5-FU treatment in patients with colorectal adenocarcinoma.
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, South Korea.
authors.forename: Dan-Ni
authors.initials: DN
authors.lastname: Ren
authors.forename: Ik-Yong
authors.initials: IY
authors.lastname: Kim
authors.forename: Sang Baek
authors.initials: SB
authors.lastname: Koh
authors.forename: Sei Jin
authors.initials: SJ
authors.lastname: Chang
authors.forename: Minseob
authors.initials: M
authors.lastname: Eom
authors.forename: Sang Yeop
authors.initials: SY
authors.lastname: Yi
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Seong
authors.forename: Mi-Dong
authors.initials: MD
authors.lastname: Kim
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
authors.forename: Mee-Yon
authors.initials: MY
authors.lastname: Cho
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D004247:DNA / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D004247:DNA; D013940:Thymidylate Synthase; D005472:Fluorouracil