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Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage

INTRODUCTION: The transcription factor SOX2 has been identified as a lineage survival oncogene in squamous cell carcinoma and copy number gain is a common event in several human malignancies including head and neck cancer. However, the regulation and function of SOX2 during carcinogenesis as well as...

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Autores principales: Thierauf, Julia, Weissinger, Stephanie E., Veit, Johannes A., Affolter, Annette, Laureano, Natalia K., Beutner, Dirk, Heiduschka, Gregor, Kadletz, Lorenz, Meyer, Moritz, Quaas, Alexander, Plinkert, Peter, Hoffmann, Thomas K., Hess, Jochen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875788/
https://www.ncbi.nlm.nih.gov/pubmed/29596469
http://dx.doi.org/10.1371/journal.pone.0194989
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author Thierauf, Julia
Weissinger, Stephanie E.
Veit, Johannes A.
Affolter, Annette
Laureano, Natalia K.
Beutner, Dirk
Heiduschka, Gregor
Kadletz, Lorenz
Meyer, Moritz
Quaas, Alexander
Plinkert, Peter
Hoffmann, Thomas K.
Hess, Jochen
author_facet Thierauf, Julia
Weissinger, Stephanie E.
Veit, Johannes A.
Affolter, Annette
Laureano, Natalia K.
Beutner, Dirk
Heiduschka, Gregor
Kadletz, Lorenz
Meyer, Moritz
Quaas, Alexander
Plinkert, Peter
Hoffmann, Thomas K.
Hess, Jochen
author_sort Thierauf, Julia
collection PubMed
description INTRODUCTION: The transcription factor SOX2 has been identified as a lineage survival oncogene in squamous cell carcinoma and copy number gain is a common event in several human malignancies including head and neck cancer. However, the regulation and function of SOX2 during carcinogenesis as well as its prognostic value appears to be highly context dependent. As an example, high SOX2 expression in lung squamous cell carcinoma (SCC) is related to a favorable prognosis, while it is associated with poor outcome in lung adenocarcinoma. More recently, higher SOX2 levels and improved survival was also reported for head and neck SCC (HNSCC), and silencing of SOX2 expression in HNSCC cell lines revealed a mesenchymal-like phenotype with prominent vimentin expression. So far, SOX2 expression and its clinical relevance for other head and neck cancers, such as adenoid cystic carcinoma (HNACC) have not been sufficiently investigated. MATERIAL AND METHODS: SOX2, vimentin and E-cadherin expression was assessed by immunohistochemical staining on serial sections from formalin fixed and paraffin embedded tissue samples of a patient cohort (n = 45) with primary ACC and correlated with patient and tumor characteristics as well as survival. RESULTS: High SOX2 expression was found in 14 (31%) primary tumor specimens and was significantly correlated with a N0 lymph node status (p = 0.04), while low SOX2 expression was correlated with a solid growth pattern (p = 0.031). Of the 45 patients, 27 tumor samples resembled an EMT-like phenotype, as assessed by high vimentin and low E-cadherin levels. However, in HNACC SOX2 levels were neither correlated with vimentin nor with E-cadherin expression, further supporting a context dependent regulation and function of SOX2 in distinct tumor entities. CONCLUSION: The absence of SOX2 was predominantly found in solid HNACC, which are characterized by a more aggressive phenotype in ACC. However, the underlying molecular mechanisms of SOX2 regulation and function in distinct HNACC subgroups remain to be fully elucidated.
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spelling pubmed-58757882018-04-13 Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage Thierauf, Julia Weissinger, Stephanie E. Veit, Johannes A. Affolter, Annette Laureano, Natalia K. Beutner, Dirk Heiduschka, Gregor Kadletz, Lorenz Meyer, Moritz Quaas, Alexander Plinkert, Peter Hoffmann, Thomas K. Hess, Jochen PLoS One Research Article INTRODUCTION: The transcription factor SOX2 has been identified as a lineage survival oncogene in squamous cell carcinoma and copy number gain is a common event in several human malignancies including head and neck cancer. However, the regulation and function of SOX2 during carcinogenesis as well as its prognostic value appears to be highly context dependent. As an example, high SOX2 expression in lung squamous cell carcinoma (SCC) is related to a favorable prognosis, while it is associated with poor outcome in lung adenocarcinoma. More recently, higher SOX2 levels and improved survival was also reported for head and neck SCC (HNSCC), and silencing of SOX2 expression in HNSCC cell lines revealed a mesenchymal-like phenotype with prominent vimentin expression. So far, SOX2 expression and its clinical relevance for other head and neck cancers, such as adenoid cystic carcinoma (HNACC) have not been sufficiently investigated. MATERIAL AND METHODS: SOX2, vimentin and E-cadherin expression was assessed by immunohistochemical staining on serial sections from formalin fixed and paraffin embedded tissue samples of a patient cohort (n = 45) with primary ACC and correlated with patient and tumor characteristics as well as survival. RESULTS: High SOX2 expression was found in 14 (31%) primary tumor specimens and was significantly correlated with a N0 lymph node status (p = 0.04), while low SOX2 expression was correlated with a solid growth pattern (p = 0.031). Of the 45 patients, 27 tumor samples resembled an EMT-like phenotype, as assessed by high vimentin and low E-cadherin levels. However, in HNACC SOX2 levels were neither correlated with vimentin nor with E-cadherin expression, further supporting a context dependent regulation and function of SOX2 in distinct tumor entities. CONCLUSION: The absence of SOX2 was predominantly found in solid HNACC, which are characterized by a more aggressive phenotype in ACC. However, the underlying molecular mechanisms of SOX2 regulation and function in distinct HNACC subgroups remain to be fully elucidated. Public Library of Science 2018-03-29 /pmc/articles/PMC5875788/ /pubmed/29596469 http://dx.doi.org/10.1371/journal.pone.0194989 Text en © 2018 Thierauf 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
Thierauf, Julia
Weissinger, Stephanie E.
Veit, Johannes A.
Affolter, Annette
Laureano, Natalia K.
Beutner, Dirk
Heiduschka, Gregor
Kadletz, Lorenz
Meyer, Moritz
Quaas, Alexander
Plinkert, Peter
Hoffmann, Thomas K.
Hess, Jochen
Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
title Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
title_full Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
title_fullStr Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
title_full_unstemmed Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
title_short Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
title_sort low sox2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875788/
https://www.ncbi.nlm.nih.gov/pubmed/29596469
http://dx.doi.org/10.1371/journal.pone.0194989
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