High pretherapeutic thymidylate synthetase and MRP-1 protein levels are associated with nonresponse to neoadjuvant chemotherapy in oesophageal adenocarcinoma patients

Background The aim of this study was to determine whether pretherapeutic protein expression levels of the excision repair cross-complementing (ERCC1) enzyme, thymidylate synthetase (TS), multidrug-resistance protein 1 (MRP-1) and P-glycoprotein (P-gp) are associated with tumour response to cisplatin...

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Main Authors: Langer, Rupert (Author) , Ott, Katja (Author) , Feith, Marcus (Author) , Lordick, Florian (Author) , Specht, Katja (Author) , Becker, Karen (Author) , Hofler, Heinz (Author)
Format: Article (Journal)
Language:English
Published: 29 June 2010
In: Journal of surgical oncology
Year: 2010, Volume: 102, Issue: 5, Pages: 503-508
ISSN:1096-9098
DOI:10.1002/jso.21641
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/jso.21641
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jso.21641
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Author Notes:Rupert Langer, Katja Ott, Marcus Feith, Florian Lordick, Katja Specht, Karen Becker, and Heinz Hofler
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Summary:Background The aim of this study was to determine whether pretherapeutic protein expression levels of the excision repair cross-complementing (ERCC1) enzyme, thymidylate synthetase (TS), multidrug-resistance protein 1 (MRP-1) and P-glycoprotein (P-gp) are associated with tumour response to cisplatin and fluorouracil (5-FU)-based neoadjuvant chemotherapy in oesophageal adenocarcinomas Methods The expression levels of ERCC1, TS, MDR-1 and P-gp were determined immunohistochemically in pretherapeutic tumour biopsies from 40 oesophageal adenocarcinoma patients and were correlated with histopathological tumour regression and with patient survival. Protein expression was compared to mRNA data, which was previously published for ERCC1, TS and MRP-1 and newly determined for the purpose of this study for MDR-1/P-gp. Results High-TS and -MRP-1 protein expression was correlated with tumour non-response to chemotherapy (P = 0.001 and P = 0.036, respectively). For ERCC-1 and P-gp, no association between pretherapeutic protein expression and response was found. There was no correlation between mRNA levels and protein expression for all investigated markers. Survival analysis revealed a trend towards increased survival for low-ERCC-1 expression (P = 0.079). Conclusions The pattern of pretherapeutic expression of TS and MRP-1 is related to chemotherapy response in oesophageal adenocarcinoma patients. Immunohistochemical assessment of these markers may be helpful for response prediction.
Item Description:Gesehen am 09.03.2023
Physical Description:Online Resource
ISSN:1096-9098
DOI:10.1002/jso.21641