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Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry

PURPOSE: Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response....

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Autores principales: van der Ploeg, Phyllis, van Lieshout, Laura A. M., van de Stolpe, Anja, Bosch, Steven L., Lentjes-Beer, Marjolein H. F. M., Bekkers, Ruud L. M., Piek, Jurgen M. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338831/
https://www.ncbi.nlm.nih.gov/pubmed/33723801
http://dx.doi.org/10.1007/s13402-021-00600-5
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author van der Ploeg, Phyllis
van Lieshout, Laura A. M.
van de Stolpe, Anja
Bosch, Steven L.
Lentjes-Beer, Marjolein H. F. M.
Bekkers, Ruud L. M.
Piek, Jurgen M. J.
author_facet van der Ploeg, Phyllis
van Lieshout, Laura A. M.
van de Stolpe, Anja
Bosch, Steven L.
Lentjes-Beer, Marjolein H. F. M.
Bekkers, Ruud L. M.
Piek, Jurgen M. J.
author_sort van der Ploeg, Phyllis
collection PubMed
description PURPOSE: Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response. To determine the accuracy of ER protein expression as a marker for ER signaling pathway activity, we aimed to correlate ER protein expression to functional ER signaling pathway activity in HGSC. METHODS: Immunohistochemical ER protein expression was visually scored using total percentages of stained tumor cells and histoscores. Subsequently, mRNA was extracted, and RT-qPCR analysis was performed. Functional ER pathway activity was assessed by a computational Bayesian model inferring ER signaling pathway activity from mRNA levels of ER-specific target genes. RESULTS: Our analysis of 29 HGSCs shows that neither total percentage of ER protein expression, nor ER histoscores are significantly correlated to ER signaling pathway activity (respectively, p = 0.473 and p = 0.606). Classification of HGSC into three groups based on ER histoscores 0–100 (n = 6), 101–200 (n = 15) and 201–300 (n = 8) resulted in comparable mean ER signaling pathway activity among the groups (p = 0.356). Several samples in the higher ER histoscore groups had low ER signaling pathway activity, indicating that nuclear ER protein expression is not sufficient to describe transcriptional ER activation. CONCLUSION: Positive immunohistochemical ER staining is not always indicative of an active ER signaling pathway and is, therefore, a poor predictor of anti-estrogen response. Further research is needed to prove the predictive value of ER signaling pathway activity regarding anti-estrogen sensitivity in HGSC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-021-00600-5.
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spelling pubmed-83388312021-08-20 Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry van der Ploeg, Phyllis van Lieshout, Laura A. M. van de Stolpe, Anja Bosch, Steven L. Lentjes-Beer, Marjolein H. F. M. Bekkers, Ruud L. M. Piek, Jurgen M. J. Cell Oncol (Dordr) Short Communication PURPOSE: Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response. To determine the accuracy of ER protein expression as a marker for ER signaling pathway activity, we aimed to correlate ER protein expression to functional ER signaling pathway activity in HGSC. METHODS: Immunohistochemical ER protein expression was visually scored using total percentages of stained tumor cells and histoscores. Subsequently, mRNA was extracted, and RT-qPCR analysis was performed. Functional ER pathway activity was assessed by a computational Bayesian model inferring ER signaling pathway activity from mRNA levels of ER-specific target genes. RESULTS: Our analysis of 29 HGSCs shows that neither total percentage of ER protein expression, nor ER histoscores are significantly correlated to ER signaling pathway activity (respectively, p = 0.473 and p = 0.606). Classification of HGSC into three groups based on ER histoscores 0–100 (n = 6), 101–200 (n = 15) and 201–300 (n = 8) resulted in comparable mean ER signaling pathway activity among the groups (p = 0.356). Several samples in the higher ER histoscore groups had low ER signaling pathway activity, indicating that nuclear ER protein expression is not sufficient to describe transcriptional ER activation. CONCLUSION: Positive immunohistochemical ER staining is not always indicative of an active ER signaling pathway and is, therefore, a poor predictor of anti-estrogen response. Further research is needed to prove the predictive value of ER signaling pathway activity regarding anti-estrogen sensitivity in HGSC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-021-00600-5. Springer Netherlands 2021-03-16 2021 /pmc/articles/PMC8338831/ /pubmed/33723801 http://dx.doi.org/10.1007/s13402-021-00600-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Short Communication
van der Ploeg, Phyllis
van Lieshout, Laura A. M.
van de Stolpe, Anja
Bosch, Steven L.
Lentjes-Beer, Marjolein H. F. M.
Bekkers, Ruud L. M.
Piek, Jurgen M. J.
Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
title Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
title_full Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
title_fullStr Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
title_full_unstemmed Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
title_short Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
title_sort functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338831/
https://www.ncbi.nlm.nih.gov/pubmed/33723801
http://dx.doi.org/10.1007/s13402-021-00600-5
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