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Cellular Oncology
Published in: Cellular Oncology 1/2014

Open Access 01-02-2014 | Original Paper

Thymidylate synthase expression and p21WAF1/p53 phenotype of colon cancers identify patients who may benefit from 5-fluorouracil based therapy

Authors: Violetta Sulzyc-Bielicka, Pawel Domagala, Dariusz Bielicki, Krzysztof Safranow, Wenancjusz Domagala

Published in: Cellular Oncology | Issue 1/2014

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Abstract

Background

Studies on the expression of thymidylate synthase (TS) in colorectal cancers (CRCs) have failed to provide unequivocal prognostic or predictive information. Here, we assessed the prognostic significance of TS expression in Astler-Coller stage B2 and C CRCs defined by a p21WAF1/p53 immunophenotype in patients subjected to 5-fluorouracil (5FU)-based adjuvant therapy.

Methods

A cohort of 189 CRCs was asssessed for TS, p21WAF1 and p53 expression on tissue microarrays using immunohistochemistry, and associations with disease-free survival (DFS) and overall survival (OS) of the patients were assessed using univariate and multivariate analyses.

Results

TS expression led to the stratification of patients with colon cancer, but not rectal cancer, with immunophenotypes other than p21WAF1+/p53- (referred to as P&P) into subgroups characterized by a worse (P&P TS+) and a better (P&P TS-) DFS and OS, in univariate (P = 0.006 and P = 0.005, respectively) and multivariate (P = 0.0004 and P = 0.002, respectively) analyses. The p21WAF1+/p53- immunophenotype was associated with a favorable prognosis, irrespective of TS expression.

Conclusions

The strong association observed between the P&P TS+ immunophenotype and a worse DFS and OS suggests a predictive significance of TS expression for 5FU-based adjuvant therapy in patients with colon cancers exhibiting the P&P immunophenotype. In addition, our findings suggest that the appropriate target for assessment of TS expression as a prognostic/predictive marker is a subgroup of colon cancers with an immunophenotype other than p21WAF1+/p53-, and that only in this subgroup high TS expression is associated with an unfavorable DFS and OS. Therefore, we suggest that assessing TS expression in conjunction with p21WAF1/p53 immunophenotyping of colon cancers may improve the selection of patients suitable for 5FU-based adjuvant chemotherapy.
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Metadata
Title
Thymidylate synthase expression and p21WAF1/p53 phenotype of colon cancers identify patients who may benefit from 5-fluorouracil based therapy
Authors
Violetta Sulzyc-Bielicka
Pawel Domagala
Dariusz Bielicki
Krzysztof Safranow
Wenancjusz Domagala
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 1/2014
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-013-0159-z

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