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Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma

BACKGROUND: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenoca...

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Autores principales: Borg, David, Hedner, Charlotta, Nodin, Björn, Larsson, Anna, Johnsson, Anders, Eberhard, Jakob, Jirström, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966733/
https://www.ncbi.nlm.nih.gov/pubmed/27478410
http://dx.doi.org/10.1186/s12907-016-0034-8
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author Borg, David
Hedner, Charlotta
Nodin, Björn
Larsson, Anna
Johnsson, Anders
Eberhard, Jakob
Jirström, Karin
author_facet Borg, David
Hedner, Charlotta
Nodin, Björn
Larsson, Anna
Johnsson, Anders
Eberhard, Jakob
Jirström, Karin
author_sort Borg, David
collection PubMed
description BACKGROUND: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma. METHODS: The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor. RESULTS: In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039). CONCLUSIONS: In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12907-016-0034-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-49667332016-07-30 Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma Borg, David Hedner, Charlotta Nodin, Björn Larsson, Anna Johnsson, Anders Eberhard, Jakob Jirström, Karin BMC Clin Pathol Research Article BACKGROUND: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma. METHODS: The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor. RESULTS: In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039). CONCLUSIONS: In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12907-016-0034-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-29 /pmc/articles/PMC4966733/ /pubmed/27478410 http://dx.doi.org/10.1186/s12907-016-0034-8 Text en © The Author(s). 2016 Open AccessThis 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
Borg, David
Hedner, Charlotta
Nodin, Björn
Larsson, Anna
Johnsson, Anders
Eberhard, Jakob
Jirström, Karin
Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
title Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
title_full Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
title_fullStr Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
title_full_unstemmed Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
title_short Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
title_sort expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966733/
https://www.ncbi.nlm.nih.gov/pubmed/27478410
http://dx.doi.org/10.1186/s12907-016-0034-8
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