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p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from th...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073933/ https://www.ncbi.nlm.nih.gov/pubmed/36948887 http://dx.doi.org/10.1002/cjp2.311 |
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author | Köbel, Martin Kang, Eun‐Young Weir, Ashley Rambau, Peter F Lee, Cheng‐Han Nelson, Gregg S Ghatage, Prafull Meagher, Nicola S Riggan, Marjorie J Alsop, Jennifer Anglesio, Michael S Beckmann, Matthias W Bisinotto, Christiani Boisen, Michelle Boros, Jessica Brand, Alison H Brooks‐Wilson, Angela Carney, Michael E Coulson, Penny Courtney‐Brooks, Madeleine Cushing‐Haugen, Kara L Cybulski, Cezary Deen, Suha El‐Bahrawy, Mona A Elishaev, Esther Erber, Ramona Fereday, Sian Fischer, Anna Gayther, Simon A Barquin‐Garcia, Arantzazu Gentry‐Maharaj, Aleksandra Gilks, C Blake Gronwald, Helena Grube, Marcel Harnett, Paul R Harris, Holly R Hartkopf, Andreas D Hartmann, Arndt Hein, Alexander Hendley, Joy Hernandez, Brenda Y Huang, Yajue Jakubowska, Anna Jimenez‐Linan, Mercedes Jones, Michael E Kennedy, Catherine J Kluz, Tomasz Koziak, Jennifer M Lesnock, Jaime Lester, Jenny Lubiński, Jan Longacre, Teri A Lycke, Maria Mateoiu, Constantina McCauley, Bryan M McGuire, Valerie Ney, Britta Olawaiye, Alexander Orsulic, Sandra Osorio, Ana Paz‐Ares, Luis Ramón y Cajal, Teresa Rothstein, Joseph H Ruebner, Matthias Schoemaker, Minouk J Shah, Mitul Sharma, Raghwa Sherman, Mark E Shvetsov, Yurii B Singh, Naveena Steed, Helen Storr, Sarah J Talhouk, Aline Traficante, Nadia Wang, Chen Whittemore, Alice S Widschwendter, Martin Wilkens, Lynne R Winham, Stacey J Benitez, Javier Berchuck, Andrew Bowtell, David D Candido dos Reis, Francisco J Campbell, Ian Cook, Linda S DeFazio, Anna Doherty, Jennifer A Fasching, Peter A Fortner, Renée T García, María J Goodman, Marc T Goode, Ellen L Gronwald, Jacek Huntsman, David G Karlan, Beth Y Kelemen, Linda E Kommoss, Stefan Le, Nhu D Martin, Stewart G Menon, Usha Modugno, Francesmary Pharoah, Paul DP Schildkraut, Joellen M Sieh, Weiva Staebler, Annette Sundfeldt, Karin Swerdlow, Anthony J Ramus, Susan J Brenton, James D |
author_facet | Köbel, Martin Kang, Eun‐Young Weir, Ashley Rambau, Peter F Lee, Cheng‐Han Nelson, Gregg S Ghatage, Prafull Meagher, Nicola S Riggan, Marjorie J Alsop, Jennifer Anglesio, Michael S Beckmann, Matthias W Bisinotto, Christiani Boisen, Michelle Boros, Jessica Brand, Alison H Brooks‐Wilson, Angela Carney, Michael E Coulson, Penny Courtney‐Brooks, Madeleine Cushing‐Haugen, Kara L Cybulski, Cezary Deen, Suha El‐Bahrawy, Mona A Elishaev, Esther Erber, Ramona Fereday, Sian Fischer, Anna Gayther, Simon A Barquin‐Garcia, Arantzazu Gentry‐Maharaj, Aleksandra Gilks, C Blake Gronwald, Helena Grube, Marcel Harnett, Paul R Harris, Holly R Hartkopf, Andreas D Hartmann, Arndt Hein, Alexander Hendley, Joy Hernandez, Brenda Y Huang, Yajue Jakubowska, Anna Jimenez‐Linan, Mercedes Jones, Michael E Kennedy, Catherine J Kluz, Tomasz Koziak, Jennifer M Lesnock, Jaime Lester, Jenny Lubiński, Jan Longacre, Teri A Lycke, Maria Mateoiu, Constantina McCauley, Bryan M McGuire, Valerie Ney, Britta Olawaiye, Alexander Orsulic, Sandra Osorio, Ana Paz‐Ares, Luis Ramón y Cajal, Teresa Rothstein, Joseph H Ruebner, Matthias Schoemaker, Minouk J Shah, Mitul Sharma, Raghwa Sherman, Mark E Shvetsov, Yurii B Singh, Naveena Steed, Helen Storr, Sarah J Talhouk, Aline Traficante, Nadia Wang, Chen Whittemore, Alice S Widschwendter, Martin Wilkens, Lynne R Winham, Stacey J Benitez, Javier Berchuck, Andrew Bowtell, David D Candido dos Reis, Francisco J Campbell, Ian Cook, Linda S DeFazio, Anna Doherty, Jennifer A Fasching, Peter A Fortner, Renée T García, María J Goodman, Marc T Goode, Ellen L Gronwald, Jacek Huntsman, David G Karlan, Beth Y Kelemen, Linda E Kommoss, Stefan Le, Nhu D Martin, Stewart G Menon, Usha Modugno, Francesmary Pharoah, Paul DP Schildkraut, Joellen M Sieh, Weiva Staebler, Annette Sundfeldt, Karin Swerdlow, Anthony J Ramus, Susan J Brenton, James D |
author_sort | Köbel, Martin |
collection | PubMed |
description | Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC. |
format | Online Article Text |
id | pubmed-10073933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100739332023-04-06 p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study Köbel, Martin Kang, Eun‐Young Weir, Ashley Rambau, Peter F Lee, Cheng‐Han Nelson, Gregg S Ghatage, Prafull Meagher, Nicola S Riggan, Marjorie J Alsop, Jennifer Anglesio, Michael S Beckmann, Matthias W Bisinotto, Christiani Boisen, Michelle Boros, Jessica Brand, Alison H Brooks‐Wilson, Angela Carney, Michael E Coulson, Penny Courtney‐Brooks, Madeleine Cushing‐Haugen, Kara L Cybulski, Cezary Deen, Suha El‐Bahrawy, Mona A Elishaev, Esther Erber, Ramona Fereday, Sian Fischer, Anna Gayther, Simon A Barquin‐Garcia, Arantzazu Gentry‐Maharaj, Aleksandra Gilks, C Blake Gronwald, Helena Grube, Marcel Harnett, Paul R Harris, Holly R Hartkopf, Andreas D Hartmann, Arndt Hein, Alexander Hendley, Joy Hernandez, Brenda Y Huang, Yajue Jakubowska, Anna Jimenez‐Linan, Mercedes Jones, Michael E Kennedy, Catherine J Kluz, Tomasz Koziak, Jennifer M Lesnock, Jaime Lester, Jenny Lubiński, Jan Longacre, Teri A Lycke, Maria Mateoiu, Constantina McCauley, Bryan M McGuire, Valerie Ney, Britta Olawaiye, Alexander Orsulic, Sandra Osorio, Ana Paz‐Ares, Luis Ramón y Cajal, Teresa Rothstein, Joseph H Ruebner, Matthias Schoemaker, Minouk J Shah, Mitul Sharma, Raghwa Sherman, Mark E Shvetsov, Yurii B Singh, Naveena Steed, Helen Storr, Sarah J Talhouk, Aline Traficante, Nadia Wang, Chen Whittemore, Alice S Widschwendter, Martin Wilkens, Lynne R Winham, Stacey J Benitez, Javier Berchuck, Andrew Bowtell, David D Candido dos Reis, Francisco J Campbell, Ian Cook, Linda S DeFazio, Anna Doherty, Jennifer A Fasching, Peter A Fortner, Renée T García, María J Goodman, Marc T Goode, Ellen L Gronwald, Jacek Huntsman, David G Karlan, Beth Y Kelemen, Linda E Kommoss, Stefan Le, Nhu D Martin, Stewart G Menon, Usha Modugno, Francesmary Pharoah, Paul DP Schildkraut, Joellen M Sieh, Weiva Staebler, Annette Sundfeldt, Karin Swerdlow, Anthony J Ramus, Susan J Brenton, James D J Pathol Clin Res Original Articles Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC. John Wiley & Sons, Inc. 2023-03-22 /pmc/articles/PMC10073933/ /pubmed/36948887 http://dx.doi.org/10.1002/cjp2.311 Text en © 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Köbel, Martin Kang, Eun‐Young Weir, Ashley Rambau, Peter F Lee, Cheng‐Han Nelson, Gregg S Ghatage, Prafull Meagher, Nicola S Riggan, Marjorie J Alsop, Jennifer Anglesio, Michael S Beckmann, Matthias W Bisinotto, Christiani Boisen, Michelle Boros, Jessica Brand, Alison H Brooks‐Wilson, Angela Carney, Michael E Coulson, Penny Courtney‐Brooks, Madeleine Cushing‐Haugen, Kara L Cybulski, Cezary Deen, Suha El‐Bahrawy, Mona A Elishaev, Esther Erber, Ramona Fereday, Sian Fischer, Anna Gayther, Simon A Barquin‐Garcia, Arantzazu Gentry‐Maharaj, Aleksandra Gilks, C Blake Gronwald, Helena Grube, Marcel Harnett, Paul R Harris, Holly R Hartkopf, Andreas D Hartmann, Arndt Hein, Alexander Hendley, Joy Hernandez, Brenda Y Huang, Yajue Jakubowska, Anna Jimenez‐Linan, Mercedes Jones, Michael E Kennedy, Catherine J Kluz, Tomasz Koziak, Jennifer M Lesnock, Jaime Lester, Jenny Lubiński, Jan Longacre, Teri A Lycke, Maria Mateoiu, Constantina McCauley, Bryan M McGuire, Valerie Ney, Britta Olawaiye, Alexander Orsulic, Sandra Osorio, Ana Paz‐Ares, Luis Ramón y Cajal, Teresa Rothstein, Joseph H Ruebner, Matthias Schoemaker, Minouk J Shah, Mitul Sharma, Raghwa Sherman, Mark E Shvetsov, Yurii B Singh, Naveena Steed, Helen Storr, Sarah J Talhouk, Aline Traficante, Nadia Wang, Chen Whittemore, Alice S Widschwendter, Martin Wilkens, Lynne R Winham, Stacey J Benitez, Javier Berchuck, Andrew Bowtell, David D Candido dos Reis, Francisco J Campbell, Ian Cook, Linda S DeFazio, Anna Doherty, Jennifer A Fasching, Peter A Fortner, Renée T García, María J Goodman, Marc T Goode, Ellen L Gronwald, Jacek Huntsman, David G Karlan, Beth Y Kelemen, Linda E Kommoss, Stefan Le, Nhu D Martin, Stewart G Menon, Usha Modugno, Francesmary Pharoah, Paul DP Schildkraut, Joellen M Sieh, Weiva Staebler, Annette Sundfeldt, Karin Swerdlow, Anthony J Ramus, Susan J Brenton, James D p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study |
title | p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study |
title_full | p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study |
title_fullStr | p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study |
title_full_unstemmed | p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study |
title_short | p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study |
title_sort | p53 and ovarian carcinoma survival: an ovarian tumor tissue analysis consortium study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073933/ https://www.ncbi.nlm.nih.gov/pubmed/36948887 http://dx.doi.org/10.1002/cjp2.311 |
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