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Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients

High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in a...

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Autores principales: Mignogna, Chiara, Staropoli, Nicoletta, Botta, Cirino, De Marco, Carmela, Rizzuto, Antonia, Morelli, Michele, Di Cello, Annalisa, Franco, Renato, Camastra, Caterina, Presta, Ivan, Malara, Natalia, Salvino, Angela, Tassone, Pierfrancesco, Tagliaferri, Pierosandro, Barni, Tullio, Donato, Giuseppe, Di Vito, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875597/
https://www.ncbi.nlm.nih.gov/pubmed/27209210
http://dx.doi.org/10.1186/s13048-016-0238-7
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author Mignogna, Chiara
Staropoli, Nicoletta
Botta, Cirino
De Marco, Carmela
Rizzuto, Antonia
Morelli, Michele
Di Cello, Annalisa
Franco, Renato
Camastra, Caterina
Presta, Ivan
Malara, Natalia
Salvino, Angela
Tassone, Pierfrancesco
Tagliaferri, Pierosandro
Barni, Tullio
Donato, Giuseppe
Di Vito, Anna
author_facet Mignogna, Chiara
Staropoli, Nicoletta
Botta, Cirino
De Marco, Carmela
Rizzuto, Antonia
Morelli, Michele
Di Cello, Annalisa
Franco, Renato
Camastra, Caterina
Presta, Ivan
Malara, Natalia
Salvino, Angela
Tassone, Pierfrancesco
Tagliaferri, Pierosandro
Barni, Tullio
Donato, Giuseppe
Di Vito, Anna
author_sort Mignogna, Chiara
collection PubMed
description High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10–0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0238-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-48755972016-05-22 Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients Mignogna, Chiara Staropoli, Nicoletta Botta, Cirino De Marco, Carmela Rizzuto, Antonia Morelli, Michele Di Cello, Annalisa Franco, Renato Camastra, Caterina Presta, Ivan Malara, Natalia Salvino, Angela Tassone, Pierfrancesco Tagliaferri, Pierosandro Barni, Tullio Donato, Giuseppe Di Vito, Anna J Ovarian Res Brief Communication High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10–0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0238-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-21 /pmc/articles/PMC4875597/ /pubmed/27209210 http://dx.doi.org/10.1186/s13048-016-0238-7 Text en © Mignogna et al. 2016 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 Brief Communication
Mignogna, Chiara
Staropoli, Nicoletta
Botta, Cirino
De Marco, Carmela
Rizzuto, Antonia
Morelli, Michele
Di Cello, Annalisa
Franco, Renato
Camastra, Caterina
Presta, Ivan
Malara, Natalia
Salvino, Angela
Tassone, Pierfrancesco
Tagliaferri, Pierosandro
Barni, Tullio
Donato, Giuseppe
Di Vito, Anna
Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
title Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
title_full Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
title_fullStr Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
title_full_unstemmed Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
title_short Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
title_sort aurora kinase a expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875597/
https://www.ncbi.nlm.nih.gov/pubmed/27209210
http://dx.doi.org/10.1186/s13048-016-0238-7
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