Cargando…

Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure

OBJECTIVES: The aim of the study was to evaluate whether HPV associated OPSCC with tobacco exposure follows a different carcinogenic pathway compared to HPV associated OPSCC without tobacco exposure and to investigate its prognostic significance. The question was addressed with focus on components o...

Descripción completa

Detalles Bibliográficos
Autores principales: Kiessling, Si‐Young, Broglie, Martina Anja, Soltermann, Alex, Huber, Gerhard Frank, Stoeckli, Sandro Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119789/
https://www.ncbi.nlm.nih.gov/pubmed/30186959
http://dx.doi.org/10.1002/lio2.175
_version_ 1783352133813272576
author Kiessling, Si‐Young
Broglie, Martina Anja
Soltermann, Alex
Huber, Gerhard Frank
Stoeckli, Sandro Johannes
author_facet Kiessling, Si‐Young
Broglie, Martina Anja
Soltermann, Alex
Huber, Gerhard Frank
Stoeckli, Sandro Johannes
author_sort Kiessling, Si‐Young
collection PubMed
description OBJECTIVES: The aim of the study was to evaluate whether HPV associated OPSCC with tobacco exposure follows a different carcinogenic pathway compared to HPV associated OPSCC without tobacco exposure and to investigate its prognostic significance. The question was addressed with focus on components of the PI3K pathway. METHODS: 184 patients with newly diagnosed OPSCC treated with curative intent were consecutively enrolled. The expression level of p16, p53, PI3K, mTOR, and PTEN was assessed by immunohistochemistry and analyzed in relation to the risk factors HPV status and tobacco exposure. RESULTS: 94 of 184 (51%) patients were p16 positive, p53 overexpression was detected in 48 of 184 (26%) cases. PI3K overexpression with 70 of 184 (38%) cases was significantly higher in p16 positive tumors. mTOR overexpression was present in 90 of 184 (49%) cases and significantly higher in p16 negative tumors. PTEN loss was found in 42 of 184 (23%) cases without association to p16 expression. p16 positive OPSCC showed lower rates of p53 expression and mTOR expression as well as higher rates of PI3K expression irrespective of tobacco exposure. Survival analysis showed a distinct intermediate survival rate of p16 positive smokers. The markers PI3K, mTOR, and PTEN did not have a significant impact on survival. CONCLUSION: HPV associated OPSCC with tobacco exposure follows the same expression level of the PI3K pathway as HPV associated OPSCC without tobacco exposure. The impaired survival rate of the intermediate risk group cannot be explained by different expression patterns of PI3K, mTOR, and PTEN. LEVEL OF EVIDENCE: 2b
format Online
Article
Text
id pubmed-6119789
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-61197892018-09-05 Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure Kiessling, Si‐Young Broglie, Martina Anja Soltermann, Alex Huber, Gerhard Frank Stoeckli, Sandro Johannes Laryngoscope Investig Otolaryngol Head and Neck, and Tumor Biology OBJECTIVES: The aim of the study was to evaluate whether HPV associated OPSCC with tobacco exposure follows a different carcinogenic pathway compared to HPV associated OPSCC without tobacco exposure and to investigate its prognostic significance. The question was addressed with focus on components of the PI3K pathway. METHODS: 184 patients with newly diagnosed OPSCC treated with curative intent were consecutively enrolled. The expression level of p16, p53, PI3K, mTOR, and PTEN was assessed by immunohistochemistry and analyzed in relation to the risk factors HPV status and tobacco exposure. RESULTS: 94 of 184 (51%) patients were p16 positive, p53 overexpression was detected in 48 of 184 (26%) cases. PI3K overexpression with 70 of 184 (38%) cases was significantly higher in p16 positive tumors. mTOR overexpression was present in 90 of 184 (49%) cases and significantly higher in p16 negative tumors. PTEN loss was found in 42 of 184 (23%) cases without association to p16 expression. p16 positive OPSCC showed lower rates of p53 expression and mTOR expression as well as higher rates of PI3K expression irrespective of tobacco exposure. Survival analysis showed a distinct intermediate survival rate of p16 positive smokers. The markers PI3K, mTOR, and PTEN did not have a significant impact on survival. CONCLUSION: HPV associated OPSCC with tobacco exposure follows the same expression level of the PI3K pathway as HPV associated OPSCC without tobacco exposure. The impaired survival rate of the intermediate risk group cannot be explained by different expression patterns of PI3K, mTOR, and PTEN. LEVEL OF EVIDENCE: 2b John Wiley and Sons Inc. 2018-08-09 /pmc/articles/PMC6119789/ /pubmed/30186959 http://dx.doi.org/10.1002/lio2.175 Text en © 2018 The Authors Laryngoscope Investigative Otolaryngology published by Wiley Periodicals, Inc. on behalf of The Triological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Head and Neck, and Tumor Biology
Kiessling, Si‐Young
Broglie, Martina Anja
Soltermann, Alex
Huber, Gerhard Frank
Stoeckli, Sandro Johannes
Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure
title Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure
title_full Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure
title_fullStr Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure
title_full_unstemmed Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure
title_short Comparison of PI3K Pathway in HPV‐Associated Oropharyngeal Cancer With and Without Tobacco Exposure
title_sort comparison of pi3k pathway in hpv‐associated oropharyngeal cancer with and without tobacco exposure
topic Head and Neck, and Tumor Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119789/
https://www.ncbi.nlm.nih.gov/pubmed/30186959
http://dx.doi.org/10.1002/lio2.175
work_keys_str_mv AT kiesslingsiyoung comparisonofpi3kpathwayinhpvassociatedoropharyngealcancerwithandwithouttobaccoexposure
AT brogliemartinaanja comparisonofpi3kpathwayinhpvassociatedoropharyngealcancerwithandwithouttobaccoexposure
AT soltermannalex comparisonofpi3kpathwayinhpvassociatedoropharyngealcancerwithandwithouttobaccoexposure
AT hubergerhardfrank comparisonofpi3kpathwayinhpvassociatedoropharyngealcancerwithandwithouttobaccoexposure
AT stoecklisandrojohannes comparisonofpi3kpathwayinhpvassociatedoropharyngealcancerwithandwithouttobaccoexposure