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Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5...

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Autores principales: Paradiso, A, Simone, G, Petroni, S, Leone, B, Vallejo, C, Lacava, J, Romero, A, Machiavelli, M, Lena, M De, Allegra, C J, Johnston, P G
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363320/
https://www.ncbi.nlm.nih.gov/pubmed/10682666
http://dx.doi.org/10.1054/bjoc.1999.0964
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author Paradiso, A
Simone, G
Petroni, S
Leone, B
Vallejo, C
Lacava, J
Romero, A
Machiavelli, M
Lena, M De
Allegra, C J
Johnston, P G
author_facet Paradiso, A
Simone, G
Petroni, S
Leone, B
Vallejo, C
Lacava, J
Romero, A
Machiavelli, M
Lena, M De
Allegra, C J
Johnston, P G
author_sort Paradiso, A
collection PubMed
description The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaign
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spelling pubmed-23633202009-09-10 Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients Paradiso, A Simone, G Petroni, S Leone, B Vallejo, C Lacava, J Romero, A Machiavelli, M Lena, M De Allegra, C J Johnston, P G Br J Cancer Regular Article The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaign Nature Publishing Group 2000-02 2000-01-18 /pmc/articles/PMC2363320/ /pubmed/10682666 http://dx.doi.org/10.1054/bjoc.1999.0964 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Paradiso, A
Simone, G
Petroni, S
Leone, B
Vallejo, C
Lacava, J
Romero, A
Machiavelli, M
Lena, M De
Allegra, C J
Johnston, P G
Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
title Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
title_full Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
title_fullStr Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
title_full_unstemmed Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
title_short Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
title_sort thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363320/
https://www.ncbi.nlm.nih.gov/pubmed/10682666
http://dx.doi.org/10.1054/bjoc.1999.0964
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