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Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis

BACKGROUND: The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CR...

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Autores principales: Shigematsu, Yasuyuki, Inamura, Kentaro, Yamamoto, Noriko, Mise, Yoshihiro, Saiura, Akio, Ishikawa, Yuichi, Takahashi, Shunji, Kanda, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192098/
https://www.ncbi.nlm.nih.gov/pubmed/30326864
http://dx.doi.org/10.1186/s12885-018-4902-8
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author Shigematsu, Yasuyuki
Inamura, Kentaro
Yamamoto, Noriko
Mise, Yoshihiro
Saiura, Akio
Ishikawa, Yuichi
Takahashi, Shunji
Kanda, Hiroaki
author_facet Shigematsu, Yasuyuki
Inamura, Kentaro
Yamamoto, Noriko
Mise, Yoshihiro
Saiura, Akio
Ishikawa, Yuichi
Takahashi, Shunji
Kanda, Hiroaki
author_sort Shigematsu, Yasuyuki
collection PubMed
description BACKGROUND: The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. METHODS: A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. RESULTS: Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08–2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52–3.85; P <  0.001). In patients with CDX2-low CRC, both DFS and OS were similar between the with and without pre- or post-operative chemotherapy groups (median DFS: 243 versus 247 days; P = 0.73, median OS: 1016 versus 1363 days; P = 0.69). CONCLUSIONS: Reduced expression of CDX2 indicates poor DFS and OS, however, it might not represent chemosensitivity in patients undergoing curative liver metastasectomy. (339/350). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4902-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-61920982018-10-23 Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis Shigematsu, Yasuyuki Inamura, Kentaro Yamamoto, Noriko Mise, Yoshihiro Saiura, Akio Ishikawa, Yuichi Takahashi, Shunji Kanda, Hiroaki BMC Cancer Research Article BACKGROUND: The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. METHODS: A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. RESULTS: Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08–2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52–3.85; P <  0.001). In patients with CDX2-low CRC, both DFS and OS were similar between the with and without pre- or post-operative chemotherapy groups (median DFS: 243 versus 247 days; P = 0.73, median OS: 1016 versus 1363 days; P = 0.69). CONCLUSIONS: Reduced expression of CDX2 indicates poor DFS and OS, however, it might not represent chemosensitivity in patients undergoing curative liver metastasectomy. (339/350). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4902-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-16 /pmc/articles/PMC6192098/ /pubmed/30326864 http://dx.doi.org/10.1186/s12885-018-4902-8 Text en © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Shigematsu, Yasuyuki
Inamura, Kentaro
Yamamoto, Noriko
Mise, Yoshihiro
Saiura, Akio
Ishikawa, Yuichi
Takahashi, Shunji
Kanda, Hiroaki
Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
title Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
title_full Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
title_fullStr Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
title_full_unstemmed Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
title_short Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
title_sort impact of cdx2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192098/
https://www.ncbi.nlm.nih.gov/pubmed/30326864
http://dx.doi.org/10.1186/s12885-018-4902-8
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