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Comparative analysis of thymidylate synthase at the protein, mRNA, and DNA levels as prognostic markers in colorectal adenocarcinoma
Author(s) -
Ren DanNi,
Kim IkYong,
Koh Sang Baek,
Chang Sei Jin,
Eom Minseob,
Yi Sang Yeop,
Seong Seung Hoon,
Kim MiDong,
Bronner Mary P.,
Cho MeeYon
Publication year - 2009
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21383
Subject(s) - thymidylate synthase , colorectal cancer , medicine , adenocarcinoma , genotyping , immunohistochemistry , oncology , colorectal adenocarcinoma , messenger rna , chemotherapy , genotype , fluorouracil , pathology , gastroenterology , cancer , gene , biology , genetics
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. J. Surg. Oncol. 2009;100:546–552. © 2009 Wiley‐Liss, Inc.