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Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer

The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of...

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Autores principales: Polychronidou, Genovefa, Kotoula, Vassiliki, Manousou, Kyriaki, Kostopoulos, Ioannis, Karayannopoulou, Georgia, Vrettou, Eleni, Bobos, Mattheos, Raptou, Georgia, Efstratiou, Ioannis, Dionysopoulos, Dimitrios, Chatzopoulos, Kyriakos, Lakis, Sotirios, Chrisafi, Sofia, Tsolakidis, Dimitrios, Papanikolaou, Alexios, Dombros, Nikolaos, Fountzilas, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283658/
https://www.ncbi.nlm.nih.gov/pubmed/30521558
http://dx.doi.org/10.1371/journal.pone.0208221
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author Polychronidou, Genovefa
Kotoula, Vassiliki
Manousou, Kyriaki
Kostopoulos, Ioannis
Karayannopoulou, Georgia
Vrettou, Eleni
Bobos, Mattheos
Raptou, Georgia
Efstratiou, Ioannis
Dionysopoulos, Dimitrios
Chatzopoulos, Kyriakos
Lakis, Sotirios
Chrisafi, Sofia
Tsolakidis, Dimitrios
Papanikolaou, Alexios
Dombros, Nikolaos
Fountzilas, George
author_facet Polychronidou, Genovefa
Kotoula, Vassiliki
Manousou, Kyriaki
Kostopoulos, Ioannis
Karayannopoulou, Georgia
Vrettou, Eleni
Bobos, Mattheos
Raptou, Georgia
Efstratiou, Ioannis
Dionysopoulos, Dimitrios
Chatzopoulos, Kyriakos
Lakis, Sotirios
Chrisafi, Sofia
Tsolakidis, Dimitrios
Papanikolaou, Alexios
Dombros, Nikolaos
Fountzilas, George
author_sort Polychronidou, Genovefa
collection PubMed
description The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of endometrial cancer, in association with clinical outcome and standard clinicopathological characteristics. A total of 204 patients with histological diagnosis of endometrial cancer treated from 2004 to 2013 were included. The evaluation of protein expression was assessed by immunohistochemistry. Univariate analysis showed that higher Ki67 labeling, expression of PTEN, p16, Notch2 and Notch3 proteins, as well as MMR proficiency were associated with increased relapse and mortality rate. Additionally, Patched-1 protein expression was associated with worse DFS, while p53 overexpression was associated with worse OS. In multivariate analyses, patients with MMR proficient tumors had more than double risk for death than patients with MMR deficient (MMRd) tumors (adjusted HR = 2.19, 95% CI 1.05–4.58, p = 0.036). Jag1 positivity conferred reduced mortality risk (HR = 0.48, 95% CI 0.23–0.97, p = 0.042). However, as shown by hierarchical clustering, patients fared better when their tumors expressed high Jag1 protein in the absence of Notch2 and Notch3, while they fared worse when all three proteins were highly expressed. Patched-1 positivity conferred higher risk for relapse (HR = 2.04, 95% CI 1.05–3.96, p = 0.036). Aberrant expression of key components of the Notch and Hedgehog signaling pathways, as well as MMRd may serve as independent prognostic factors for recurrence and survival in patients with endometrial cancer.
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spelling pubmed-62836582018-12-28 Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer Polychronidou, Genovefa Kotoula, Vassiliki Manousou, Kyriaki Kostopoulos, Ioannis Karayannopoulou, Georgia Vrettou, Eleni Bobos, Mattheos Raptou, Georgia Efstratiou, Ioannis Dionysopoulos, Dimitrios Chatzopoulos, Kyriakos Lakis, Sotirios Chrisafi, Sofia Tsolakidis, Dimitrios Papanikolaou, Alexios Dombros, Nikolaos Fountzilas, George PLoS One Research Article The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of endometrial cancer, in association with clinical outcome and standard clinicopathological characteristics. A total of 204 patients with histological diagnosis of endometrial cancer treated from 2004 to 2013 were included. The evaluation of protein expression was assessed by immunohistochemistry. Univariate analysis showed that higher Ki67 labeling, expression of PTEN, p16, Notch2 and Notch3 proteins, as well as MMR proficiency were associated with increased relapse and mortality rate. Additionally, Patched-1 protein expression was associated with worse DFS, while p53 overexpression was associated with worse OS. In multivariate analyses, patients with MMR proficient tumors had more than double risk for death than patients with MMR deficient (MMRd) tumors (adjusted HR = 2.19, 95% CI 1.05–4.58, p = 0.036). Jag1 positivity conferred reduced mortality risk (HR = 0.48, 95% CI 0.23–0.97, p = 0.042). However, as shown by hierarchical clustering, patients fared better when their tumors expressed high Jag1 protein in the absence of Notch2 and Notch3, while they fared worse when all three proteins were highly expressed. Patched-1 positivity conferred higher risk for relapse (HR = 2.04, 95% CI 1.05–3.96, p = 0.036). Aberrant expression of key components of the Notch and Hedgehog signaling pathways, as well as MMRd may serve as independent prognostic factors for recurrence and survival in patients with endometrial cancer. Public Library of Science 2018-12-06 /pmc/articles/PMC6283658/ /pubmed/30521558 http://dx.doi.org/10.1371/journal.pone.0208221 Text en © 2018 Polychronidou et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Polychronidou, Genovefa
Kotoula, Vassiliki
Manousou, Kyriaki
Kostopoulos, Ioannis
Karayannopoulou, Georgia
Vrettou, Eleni
Bobos, Mattheos
Raptou, Georgia
Efstratiou, Ioannis
Dionysopoulos, Dimitrios
Chatzopoulos, Kyriakos
Lakis, Sotirios
Chrisafi, Sofia
Tsolakidis, Dimitrios
Papanikolaou, Alexios
Dombros, Nikolaos
Fountzilas, George
Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer
title Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer
title_full Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer
title_fullStr Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer
title_full_unstemmed Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer
title_short Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer
title_sort mismatch repair deficiency and aberrations in the notch and hedgehog pathways are of prognostic value in patients with endometrial cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283658/
https://www.ncbi.nlm.nih.gov/pubmed/30521558
http://dx.doi.org/10.1371/journal.pone.0208221
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