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Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
BACKGROUND: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, l...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828488/ https://www.ncbi.nlm.nih.gov/pubmed/29482584 http://dx.doi.org/10.1186/s13048-018-0389-9 |
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author | Beeghly-Fadiel, Alicia Wilson, Andrew J. Keene, Spencer El Ramahi, Meral Xu, Shu Marnett, Lawrence J. Fadare, Oluwole Crispens, Marta A. Khabele, Dineo |
author_facet | Beeghly-Fadiel, Alicia Wilson, Andrew J. Keene, Spencer El Ramahi, Meral Xu, Shu Marnett, Lawrence J. Fadare, Oluwole Crispens, Marta A. Khabele, Dineo |
author_sort | Beeghly-Fadiel, Alicia |
collection | PubMed |
description | BACKGROUND: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, low grade endometrioid and low grade serous) and type II (high grade serous and high grade endometrioid) ovarian tumors. METHODS: We developed and validated a new COX-1 antibody, and conducted immunohistochemical (IHC) staining for COX-1 and COX-2 on a tissue microarray (TMA) of 190 primary ovarian tumors. In addition to standard IHC scoring and H-scores to combine the percentage of positive cells and staining intensity, we also measured COX-1 and COX-2 mRNA expression by QPCR. High expression was defined as greater than or equal to median values. Clinical characteristics and disease outcomes were ascertained from medical records. Associations with disease-free survival (DFS) and overall survival (OS) were quantified by hazard ratios (HRs) and confidence intervals (CIs) from proportional hazards regression. RESULTS: Type I tumors had high COX-2 expression, while type II tumors had high COX-1 expression. In multivariable adjusted regression models, higher COX-1 mRNA expression was associated with shorter DFS (HR: 6.37, 95% CI: 1.84–22.01) and OS (HR: 2.26, 95% CI: 1.04–4.91), while higher H-scores for COX-2 expression were associated with shorter DFS (HR: 1.92, 95% CI: 1.06–3.49). Stratified analysis indicated that COX-2 was significantly associated with DFS among cases with Type II tumors (HR: 1.93, 95% CI: 1.06–3.53). CONCLUSIONS: These findings suggest that ovarian tumor type contributes to differences in COX expression levels and associations with survival. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13048-018-0389-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5828488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58284882018-03-01 Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors Beeghly-Fadiel, Alicia Wilson, Andrew J. Keene, Spencer El Ramahi, Meral Xu, Shu Marnett, Lawrence J. Fadare, Oluwole Crispens, Marta A. Khabele, Dineo J Ovarian Res Research BACKGROUND: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, low grade endometrioid and low grade serous) and type II (high grade serous and high grade endometrioid) ovarian tumors. METHODS: We developed and validated a new COX-1 antibody, and conducted immunohistochemical (IHC) staining for COX-1 and COX-2 on a tissue microarray (TMA) of 190 primary ovarian tumors. In addition to standard IHC scoring and H-scores to combine the percentage of positive cells and staining intensity, we also measured COX-1 and COX-2 mRNA expression by QPCR. High expression was defined as greater than or equal to median values. Clinical characteristics and disease outcomes were ascertained from medical records. Associations with disease-free survival (DFS) and overall survival (OS) were quantified by hazard ratios (HRs) and confidence intervals (CIs) from proportional hazards regression. RESULTS: Type I tumors had high COX-2 expression, while type II tumors had high COX-1 expression. In multivariable adjusted regression models, higher COX-1 mRNA expression was associated with shorter DFS (HR: 6.37, 95% CI: 1.84–22.01) and OS (HR: 2.26, 95% CI: 1.04–4.91), while higher H-scores for COX-2 expression were associated with shorter DFS (HR: 1.92, 95% CI: 1.06–3.49). Stratified analysis indicated that COX-2 was significantly associated with DFS among cases with Type II tumors (HR: 1.93, 95% CI: 1.06–3.53). CONCLUSIONS: These findings suggest that ovarian tumor type contributes to differences in COX expression levels and associations with survival. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13048-018-0389-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-27 /pmc/articles/PMC5828488/ /pubmed/29482584 http://dx.doi.org/10.1186/s13048-018-0389-9 Text en © The Author(s). 2018 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 Beeghly-Fadiel, Alicia Wilson, Andrew J. Keene, Spencer El Ramahi, Meral Xu, Shu Marnett, Lawrence J. Fadare, Oluwole Crispens, Marta A. Khabele, Dineo Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors |
title | Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors |
title_full | Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors |
title_fullStr | Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors |
title_full_unstemmed | Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors |
title_short | Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors |
title_sort | differential cyclooxygenase expression levels and survival associations in type i and type ii ovarian tumors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828488/ https://www.ncbi.nlm.nih.gov/pubmed/29482584 http://dx.doi.org/10.1186/s13048-018-0389-9 |
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