Comparative analysis of thymidylate synthase at the protein, mRNA, and DNA levels as prognostic markers in colorectal adenocarcinoma

Dan Ni Ren, Ik Yong Kim, Sang Baek Koh, Sei Jin Chang, Minseob Eom, Sang Yeop Yi, Seung Hoon Seong, Mi Dong Kim, Mary P. Bronner, Mee Yon Cho

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background and Objectives: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)546-552
Number of pages7
JournalJournal of surgical oncology
Volume100
Issue number7
DOIs
Publication statusPublished - 2009 Dec 1

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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