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Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma

Type II endometrial carcinoma mainly originates from p53 aberration. However, the detailed prognostic significance of p53 aberration in endometrial carcinoma remains to be clarified. In the present study, abnormal p53 accumulation was analyzed using immunohistochemical techniques in endometrial carc...

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Autores principales: Akiyama, Azusa, Minaguchi, Takeo, Fujieda, Kaoru, Hosokawa, Yoshihiko, Nishida, Keiko, Shikama, Ayumi, Tasaka, Nobutaka, Sakurai, Manabu, Ochi, Hiroyuki, Satoh, Toyomi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865064/
https://www.ncbi.nlm.nih.gov/pubmed/31788069
http://dx.doi.org/10.3892/ol.2019.10940
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author Akiyama, Azusa
Minaguchi, Takeo
Fujieda, Kaoru
Hosokawa, Yoshihiko
Nishida, Keiko
Shikama, Ayumi
Tasaka, Nobutaka
Sakurai, Manabu
Ochi, Hiroyuki
Satoh, Toyomi
author_facet Akiyama, Azusa
Minaguchi, Takeo
Fujieda, Kaoru
Hosokawa, Yoshihiko
Nishida, Keiko
Shikama, Ayumi
Tasaka, Nobutaka
Sakurai, Manabu
Ochi, Hiroyuki
Satoh, Toyomi
author_sort Akiyama, Azusa
collection PubMed
description Type II endometrial carcinoma mainly originates from p53 aberration. However, the detailed prognostic significance of p53 aberration in endometrial carcinoma remains to be clarified. In the present study, abnormal p53 accumulation was analyzed using immunohistochemical techniques in endometrial carcinoma samples derived from 221 consecutive patients. The expression levels of p53 were associated with clinicopathological parameters and patient survival. P53 overexpression was observed in 37/221 patients (17%), and was associated with non-endometrioid histology, post-menopause and advanced tumor stage (III/IV; P=0.0006, P=0.03 and P=0.025, respectively). Survival analysis indicated that patients with p53-overexpressing tumors exhibited poor overall survival (OS) compared with patients without p53 overexpression (P<0.000001). Univariate and multivariate analyses demonstrated that the parameters p53 overexpression, age ≥70, non-endometrioid histology and advanced stage were significant and independent prognostic factors for poor OS (P=0.00012, P=0.00048, P=0.0027 and P=0.0015, respectively). Additionally, adjuvant radiotherapy was associated with increased OS in patients without p53 overexpression. This finding was not observed for patients with adjuvant chemotherapy. In contrast to patients without p53 overexpression, patients with p53 overexpression exhibited no association with OS (P=0.02 vs. P=0.40). Notably, adjuvant radiotherapy was identified to be a significant prognostic factor for favorable OS in the subset of patients that did not exhibit p53 overexpression and received post-operative treatment (P=0.026). The findings suggested that abnormal p53 accumulation may influence patient survival via unfavorable biological tumor properties, including rapid progression and radioresistance. The present study offered valuable insights for the genome-directed management of endometrial carcinoma.
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spelling pubmed-68650642019-11-30 Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma Akiyama, Azusa Minaguchi, Takeo Fujieda, Kaoru Hosokawa, Yoshihiko Nishida, Keiko Shikama, Ayumi Tasaka, Nobutaka Sakurai, Manabu Ochi, Hiroyuki Satoh, Toyomi Oncol Lett Articles Type II endometrial carcinoma mainly originates from p53 aberration. However, the detailed prognostic significance of p53 aberration in endometrial carcinoma remains to be clarified. In the present study, abnormal p53 accumulation was analyzed using immunohistochemical techniques in endometrial carcinoma samples derived from 221 consecutive patients. The expression levels of p53 were associated with clinicopathological parameters and patient survival. P53 overexpression was observed in 37/221 patients (17%), and was associated with non-endometrioid histology, post-menopause and advanced tumor stage (III/IV; P=0.0006, P=0.03 and P=0.025, respectively). Survival analysis indicated that patients with p53-overexpressing tumors exhibited poor overall survival (OS) compared with patients without p53 overexpression (P<0.000001). Univariate and multivariate analyses demonstrated that the parameters p53 overexpression, age ≥70, non-endometrioid histology and advanced stage were significant and independent prognostic factors for poor OS (P=0.00012, P=0.00048, P=0.0027 and P=0.0015, respectively). Additionally, adjuvant radiotherapy was associated with increased OS in patients without p53 overexpression. This finding was not observed for patients with adjuvant chemotherapy. In contrast to patients without p53 overexpression, patients with p53 overexpression exhibited no association with OS (P=0.02 vs. P=0.40). Notably, adjuvant radiotherapy was identified to be a significant prognostic factor for favorable OS in the subset of patients that did not exhibit p53 overexpression and received post-operative treatment (P=0.026). The findings suggested that abnormal p53 accumulation may influence patient survival via unfavorable biological tumor properties, including rapid progression and radioresistance. The present study offered valuable insights for the genome-directed management of endometrial carcinoma. D.A. Spandidos 2019-12 2019-09-30 /pmc/articles/PMC6865064/ /pubmed/31788069 http://dx.doi.org/10.3892/ol.2019.10940 Text en Copyright: © Akiyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Articles
Akiyama, Azusa
Minaguchi, Takeo
Fujieda, Kaoru
Hosokawa, Yoshihiko
Nishida, Keiko
Shikama, Ayumi
Tasaka, Nobutaka
Sakurai, Manabu
Ochi, Hiroyuki
Satoh, Toyomi
Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
title Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
title_full Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
title_fullStr Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
title_full_unstemmed Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
title_short Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
title_sort abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865064/
https://www.ncbi.nlm.nih.gov/pubmed/31788069
http://dx.doi.org/10.3892/ol.2019.10940
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