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Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma

Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU). Nuclear expression of TS in human tissue in vivo has not been characterised and its clinicopathological correlates in malignancy are unknown. 52 cases of pri...

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Autores principales: Wong, N A C S, Brett, L, Stewart, M, Leitch, A, Longley, D B, Dunlop, M G, Johnston, P G, Lessells, A M, Jodrell, D I
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364004/
https://www.ncbi.nlm.nih.gov/pubmed/11747337
http://dx.doi.org/10.1054/bjoc.2001.2175
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author Wong, N A C S
Brett, L
Stewart, M
Leitch, A
Longley, D B
Dunlop, M G
Johnston, P G
Lessells, A M
Jodrell, D I
author_facet Wong, N A C S
Brett, L
Stewart, M
Leitch, A
Longley, D B
Dunlop, M G
Johnston, P G
Lessells, A M
Jodrell, D I
author_sort Wong, N A C S
collection PubMed
description Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU). Nuclear expression of TS in human tissue in vivo has not been characterised and its clinicopathological correlates in malignancy are unknown. 52 cases of primary colorectal carcinoma (CRC) and 24 cases of matched metastatic carcinoma were studied immunohistochemically using the monoclonal antibody TS106. The degree of nuclear TS immunostaining correlated closely with levels of TS mRNA expression amongst 10 CRCs studied. Strong nuclear immunostaining was seen in normal basal crypt colonocytes and germinal centre cells, and in a varying proportion of adenocarcinoma cells. Amongst the primary carcinomas, higher TS nuclear expression was associated with prominent extracellular mucin production and right-sided location. Higher TS nuclear expression also showed a significant association with poorer response to protracted venous infusional 5FU therapy. There was no clear association between TS nuclear expression and Ki67 or p53 expression assessed immunohistochemically. There was a strong positive correlation between TS nuclear expression in primary and metastatic CRC but the latter generally showed higher expression than matched primary tumour tissue. These findings confirm the nuclear expression of TS protein in human cells in vivo and provide new insight into how such expression may relate to the behaviour of CRCs. © 2001 Cancer Research Campaign http://www.bjcancer.com
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spelling pubmed-23640042009-09-10 Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma Wong, N A C S Brett, L Stewart, M Leitch, A Longley, D B Dunlop, M G Johnston, P G Lessells, A M Jodrell, D I Br J Cancer Regular Article Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU). Nuclear expression of TS in human tissue in vivo has not been characterised and its clinicopathological correlates in malignancy are unknown. 52 cases of primary colorectal carcinoma (CRC) and 24 cases of matched metastatic carcinoma were studied immunohistochemically using the monoclonal antibody TS106. The degree of nuclear TS immunostaining correlated closely with levels of TS mRNA expression amongst 10 CRCs studied. Strong nuclear immunostaining was seen in normal basal crypt colonocytes and germinal centre cells, and in a varying proportion of adenocarcinoma cells. Amongst the primary carcinomas, higher TS nuclear expression was associated with prominent extracellular mucin production and right-sided location. Higher TS nuclear expression also showed a significant association with poorer response to protracted venous infusional 5FU therapy. There was no clear association between TS nuclear expression and Ki67 or p53 expression assessed immunohistochemically. There was a strong positive correlation between TS nuclear expression in primary and metastatic CRC but the latter generally showed higher expression than matched primary tumour tissue. These findings confirm the nuclear expression of TS protein in human cells in vivo and provide new insight into how such expression may relate to the behaviour of CRCs. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-12 /pmc/articles/PMC2364004/ /pubmed/11747337 http://dx.doi.org/10.1054/bjoc.2001.2175 Text en Copyright © 2001 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
Wong, N A C S
Brett, L
Stewart, M
Leitch, A
Longley, D B
Dunlop, M G
Johnston, P G
Lessells, A M
Jodrell, D I
Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
title Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
title_full Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
title_fullStr Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
title_full_unstemmed Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
title_short Nuclear thymidylate synthase expression, p53 expression and 5FU response in colorectal carcinoma
title_sort nuclear thymidylate synthase expression, p53 expression and 5fu response in colorectal carcinoma
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364004/
https://www.ncbi.nlm.nih.gov/pubmed/11747337
http://dx.doi.org/10.1054/bjoc.2001.2175
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