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Thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase expression, and histological tumour regression after 5‐FU‐based neo‐adjuvant chemoradiotherapy in rectal cancer
Author(s) -
Jakob Christiane,
Aust Daniela E,
Meyer Wolfdietrich,
Baretton Gustavo B,
Schwabe Wolfgang,
Häusler Peter,
Becker Heinz,
Liersch Torsten
Publication year - 2004
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1663
Subject(s) - thymidylate synthase , dihydropyrimidine dehydrogenase , thymidine phosphorylase , chemoradiotherapy , colorectal cancer , microdissection , medicine , pathology , cancer , fluorouracil , biology , gene , biochemistry
Pre‐operative 5‐fluorouracil (5‐FU)‐based chemoradiotherapy in locally advanced rectal cancer (UICC‐II/III) may significantly reduce local tumour mass. Response to pre‐operative treatment, however, varies significantly. Thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are thought to be important predictors for the efficiency of 5‐FU‐based treatment. The aim of this study was to determine the correlation between TS‐, TP‐, and DPD‐gene expression and the response to 5‐FU‐based long‐term pre‐operative chemoradiotherapy assessed by histopathological tumour regression. Additionally, the predictive value of intra‐tumoural TS‐, TP‐, and DPD‐gene expression in pre‐operative rectal tumour biopsies was assessed by correlation with the histopathological regression grade. Formalin‐fixed, paraffin wax‐embedded pre‐operative biopsies ( n = 14) and surgical resection specimens ( n = 40) from patients with rectal carcinoma (clinical UICC stage II/III) receiving neo‐adjuvant 5‐FU‐based chemoradiotherapy were studied for TS‐, TP‐, and DPD‐gene expression by quantitative TaqMan real‐time PCR after laser microdissection. Results were compared with standardized histopathological tumour regression analysis. There was a significant association between low TS‐gene expression in pre‐operative tumour biopsies and tumour response ( p = 0.02). TS‐ and TP‐gene expression was significantly lower in resection specimens of responders than of non‐responders ( p = 0.02) when microdissection was used. Statistical significance was even higher when TS and TP were combined ( p = 0.0001). For the DPD gene, no significance was found at all. In conclusion, this study shows that TS gene expression in a pretreatment biopsy predicts the response of local rectal cancer to neo‐adjuvant 5‐FU‐based chemoradiotherapy in a high percentage. Moreover, intra‐tumoural TS‐ and TP‐gene expression in surgical rectal specimens after neo‐adjuvant chemoradiotherapy correlates significantly with histopathological tumour regression when microdissection is applied. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.