A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma

Aims and Background. Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy. Our aim was to study the expression of thymidylate synthase (TS) enzyme in pre-treatment diagnostic biopsy specimens and investigate its clinical...

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Main Authors: A. Mirza, M. Brown, C. McNulty, J. Valentine, A. Annesley, S. Galloway, I. Welch, C. M. West, S. Pritchard
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2013/502153
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author A. Mirza
M. Brown
C. McNulty
J. Valentine
A. Annesley
S. Galloway
I. Welch
C. M. West
S. Pritchard
author_facet A. Mirza
M. Brown
C. McNulty
J. Valentine
A. Annesley
S. Galloway
I. Welch
C. M. West
S. Pritchard
author_sort A. Mirza
collection DOAJ
description Aims and Background. Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy. Our aim was to study the expression of thymidylate synthase (TS) enzyme in pre-treatment diagnostic biopsy specimens and investigate its clinical usefulness. Methods. A single-centre study was carried out in 45 patients with gastric and GOJ adenocarcinoma treated with neo-adjuvant chemotherapy according to the MAGIC protocol. TS expression was determined using immunohistochemistry. >10% tumour nuclei expression of TS was used as cut-off for positivity. Results. Forty-one (91%) of the 45 tumours expressed TS. There was no association between TS expression and lymph node status (P = 0.80), histological response (P = 0.30), and recurrence (P = 0.55). On univariate analysis, only N-stage (P = 0.02) and vascular invasion (P = 0.04) were associated with a poor prognosis. Patients with negative tumour TS expression had better outcome than those with positive expression. The overall 5-year survival rate was 100% in the TS negative versus 56% in TS positive group, but the difference was not statistically significant (P = 0.17). Conclusion. TS expression should be studied in a larger series of gastro-oesophageal cancers as a potential prognostic marker of prognosis to neo-adjuvant chemotherapy.
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spelling doaj-art-ea152d8f0e5943f5950f62d7d261cad12025-08-20T03:20:39ZengWileyGastroenterology Research and Practice1687-61211687-630X2013-01-01201310.1155/2013/502153502153A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction AdenocarcinomaA. Mirza0M. Brown1C. McNulty2J. Valentine3A. Annesley4S. Galloway5I. Welch6C. M. West7S. Pritchard8Departments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKTranslational Radiobiology Group, School of Cancer and Enabling Sciences, The University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Trust, Manchester M20 4BX, UKDepartments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UKAims and Background. Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy. Our aim was to study the expression of thymidylate synthase (TS) enzyme in pre-treatment diagnostic biopsy specimens and investigate its clinical usefulness. Methods. A single-centre study was carried out in 45 patients with gastric and GOJ adenocarcinoma treated with neo-adjuvant chemotherapy according to the MAGIC protocol. TS expression was determined using immunohistochemistry. >10% tumour nuclei expression of TS was used as cut-off for positivity. Results. Forty-one (91%) of the 45 tumours expressed TS. There was no association between TS expression and lymph node status (P = 0.80), histological response (P = 0.30), and recurrence (P = 0.55). On univariate analysis, only N-stage (P = 0.02) and vascular invasion (P = 0.04) were associated with a poor prognosis. Patients with negative tumour TS expression had better outcome than those with positive expression. The overall 5-year survival rate was 100% in the TS negative versus 56% in TS positive group, but the difference was not statistically significant (P = 0.17). Conclusion. TS expression should be studied in a larger series of gastro-oesophageal cancers as a potential prognostic marker of prognosis to neo-adjuvant chemotherapy.http://dx.doi.org/10.1155/2013/502153
spellingShingle A. Mirza
M. Brown
C. McNulty
J. Valentine
A. Annesley
S. Galloway
I. Welch
C. M. West
S. Pritchard
A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma
Gastroenterology Research and Practice
title A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma
title_full A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma
title_fullStr A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma
title_full_unstemmed A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma
title_short A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma
title_sort pilot study to investigate the role of thymidylate synthase as a marker of prognosis for neoadjuvant chemotherapy in gastric and gastro oesophageal junction adenocarcinoma
url http://dx.doi.org/10.1155/2013/502153
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