A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.

BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). PATIENTS AND METHODS: A total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively plan...

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Main Authors: Popat, S, Chen, Z, Zhao, D, Pan, H, Hearle, N, Chandler, I, Shao, Y, Aherne, W, Houlston, R
Format: Journal article
Language:English
Published: 2006
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author Popat, S
Chen, Z
Zhao, D
Pan, H
Hearle, N
Chandler, I
Shao, Y
Aherne, W
Houlston, R
author_facet Popat, S
Chen, Z
Zhao, D
Pan, H
Hearle, N
Chandler, I
Shao, Y
Aherne, W
Houlston, R
author_sort Popat, S
collection OXFORD
description BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). PATIENTS AND METHODS: A total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively planned molecular substudy, and of them, 59% had rectal cancer and about 90% received adjuvant chemotherapy (either systemically or randomly allocated to intraportal 5-fluorouracil infusion or both). TS and p53 status were determined, blinded to any clinical data, by immunohistochemistry using a validated polyclonal antibody or the DO-7 clone, respectively, and their relationships with overall survival were examined. RESULTS: High TS expression was observed in 58% and overexpression of p53 in 60% of tumours. TS expression correlated with tumour stage, and p53 overexpression, with rectal cancers. There was no evidence that either marker was significantly associated with survival by either univariate (TS hazard ratio (HR) = 0.94, 95% CI 0.76-1.18 and P = 0.6 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.9) or multivariate analyses (TS HR = 0.99, 95% CI 0.79-1.25 and P = 0.9 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.8). CONCLUSIONS: Neither TS nor p53 expression has significant prognostic value in the adjuvant setting of CRC.
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spelling oxford-uuid:26cfb89a-5408-462e-866f-23c6b9846a342022-03-26T12:03:19ZA prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:26cfb89a-5408-462e-866f-23c6b9846a34EnglishSymplectic Elements at Oxford2006Popat, SChen, ZZhao, DPan, HHearle, NChandler, IShao, YAherne, WHoulston, R BACKGROUND: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). PATIENTS AND METHODS: A total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively planned molecular substudy, and of them, 59% had rectal cancer and about 90% received adjuvant chemotherapy (either systemically or randomly allocated to intraportal 5-fluorouracil infusion or both). TS and p53 status were determined, blinded to any clinical data, by immunohistochemistry using a validated polyclonal antibody or the DO-7 clone, respectively, and their relationships with overall survival were examined. RESULTS: High TS expression was observed in 58% and overexpression of p53 in 60% of tumours. TS expression correlated with tumour stage, and p53 overexpression, with rectal cancers. There was no evidence that either marker was significantly associated with survival by either univariate (TS hazard ratio (HR) = 0.94, 95% CI 0.76-1.18 and P = 0.6 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.9) or multivariate analyses (TS HR = 0.99, 95% CI 0.79-1.25 and P = 0.9 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.8). CONCLUSIONS: Neither TS nor p53 expression has significant prognostic value in the adjuvant setting of CRC.
spellingShingle Popat, S
Chen, Z
Zhao, D
Pan, H
Hearle, N
Chandler, I
Shao, Y
Aherne, W
Houlston, R
A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
title A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
title_full A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
title_fullStr A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
title_full_unstemmed A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
title_short A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
title_sort prospective blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer
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