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Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy

Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis‐promoting protein S100A4 predicts poor outcome in colorectal cancer, bu...

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Autores principales: Boye, Kjetil, Jacob, Havjin, Frikstad, Kari‐Anne M., Nesland, Jahn M., Mælandsmo, Gunhild M., Dahl, Olav, Nesbakken, Arild, Flatmark, Kjersti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971912/
https://www.ncbi.nlm.nih.gov/pubmed/27273130
http://dx.doi.org/10.1002/cam4.766
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author Boye, Kjetil
Jacob, Havjin
Frikstad, Kari‐Anne M.
Nesland, Jahn M.
Mælandsmo, Gunhild M.
Dahl, Olav
Nesbakken, Arild
Flatmark, Kjersti
author_facet Boye, Kjetil
Jacob, Havjin
Frikstad, Kari‐Anne M.
Nesland, Jahn M.
Mælandsmo, Gunhild M.
Dahl, Olav
Nesbakken, Arild
Flatmark, Kjersti
author_sort Boye, Kjetil
collection PubMed
description Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis‐promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population‐representative cohort and a randomized phase III study on adjuvant 5‐fluorouracil/levamisole. Sensitivity to treatment with 5‐fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse‐free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse‐free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5‐fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5‐fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine‐based chemotherapy is limited.
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spelling pubmed-49719122016-08-11 Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy Boye, Kjetil Jacob, Havjin Frikstad, Kari‐Anne M. Nesland, Jahn M. Mælandsmo, Gunhild M. Dahl, Olav Nesbakken, Arild Flatmark, Kjersti Cancer Med Clinical Cancer Research Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis‐promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population‐representative cohort and a randomized phase III study on adjuvant 5‐fluorouracil/levamisole. Sensitivity to treatment with 5‐fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse‐free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse‐free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5‐fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5‐fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine‐based chemotherapy is limited. John Wiley and Sons Inc. 2016-06-08 /pmc/articles/PMC4971912/ /pubmed/27273130 http://dx.doi.org/10.1002/cam4.766 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Boye, Kjetil
Jacob, Havjin
Frikstad, Kari‐Anne M.
Nesland, Jahn M.
Mælandsmo, Gunhild M.
Dahl, Olav
Nesbakken, Arild
Flatmark, Kjersti
Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
title Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
title_full Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
title_fullStr Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
title_full_unstemmed Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
title_short Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy
title_sort prognostic significance of s100a4 expression in stage ii and iii colorectal cancer: results from a population‐based series and a randomized phase iii study on adjuvant chemotherapy
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971912/
https://www.ncbi.nlm.nih.gov/pubmed/27273130
http://dx.doi.org/10.1002/cam4.766
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