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EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?

Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key ste...

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Autores principales: Cheaito, Katia A., Bahmad, Hisham F., Hadadeh, Ola, Saleh, Eman, Dagher, Christelle, Hammoud, Miza Salim, Shahait, Mohammad, Mrad, Zaki Abou, Nassif, Samer, Tawil, Ayman, Bulbul, Muhammad, Khauli, Raja, Wazzan, Wassim, Nasr, Rami, Shamseddine, Ali, Temraz, Sally, El-Sabban, Marwan E., El-Hajj, Albert, Mukherji, Deborah, Abou-Kheir, Wassim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421270/
https://www.ncbi.nlm.nih.gov/pubmed/30915272
http://dx.doi.org/10.3389/fonc.2019.00131
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author Cheaito, Katia A.
Bahmad, Hisham F.
Hadadeh, Ola
Saleh, Eman
Dagher, Christelle
Hammoud, Miza Salim
Shahait, Mohammad
Mrad, Zaki Abou
Nassif, Samer
Tawil, Ayman
Bulbul, Muhammad
Khauli, Raja
Wazzan, Wassim
Nasr, Rami
Shamseddine, Ali
Temraz, Sally
El-Sabban, Marwan E.
El-Hajj, Albert
Mukherji, Deborah
Abou-Kheir, Wassim
author_facet Cheaito, Katia A.
Bahmad, Hisham F.
Hadadeh, Ola
Saleh, Eman
Dagher, Christelle
Hammoud, Miza Salim
Shahait, Mohammad
Mrad, Zaki Abou
Nassif, Samer
Tawil, Ayman
Bulbul, Muhammad
Khauli, Raja
Wazzan, Wassim
Nasr, Rami
Shamseddine, Ali
Temraz, Sally
El-Sabban, Marwan E.
El-Hajj, Albert
Mukherji, Deborah
Abou-Kheir, Wassim
author_sort Cheaito, Katia A.
collection PubMed
description Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key step in the invasion and malignant progression of PCa. We sought to assess the co-expression of epithelial cytokeratin 8 (CK8) and mesenchymal vimentin (Vim) in locally-advanced PCa as indicators of EMT and consequently predictors of the progression status of the disease. Methods: Co-expression of CK8 and Vim was evaluated by immunofluorescence (IF) on paraffin-embedded tissue sections of 122 patients with PCa who underwent radical prostatectomies between 1998 and 2016 at the American University of Beirut Medical Center (AUBMC). EMT score was calculated accordingly and then correlated with the patients' clinicopathological parameters and PSA failure. Results: The co-expression of CK8/Vim (EMT score), was associated with increasing Gleason group. A highly significant linear association was detected wherein higher Gleason group was associated with higher mean EMT score. In addition, the median estimated biochemical recurrence-free survival for patients with < 25% EMT score was almost double that of patients with more than 25%. The validity of this score for prediction of prognosis was further demonstrated using cox regression model. Our data also confirmed that the EMT score can predict PSA failure irrespective of Gleason group, pathological stage, or surgical margins. Conclusion: This study suggests that assessment of molecular markers of EMT, particularly CK8 and Vim, in radical prostatectomy specimens, in addition to conventional clinicopathological prognostic parameters, can aid in the development of a novel system for predicting the prognosis of locally-advanced PCa.
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spelling pubmed-64212702019-03-26 EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence? Cheaito, Katia A. Bahmad, Hisham F. Hadadeh, Ola Saleh, Eman Dagher, Christelle Hammoud, Miza Salim Shahait, Mohammad Mrad, Zaki Abou Nassif, Samer Tawil, Ayman Bulbul, Muhammad Khauli, Raja Wazzan, Wassim Nasr, Rami Shamseddine, Ali Temraz, Sally El-Sabban, Marwan E. El-Hajj, Albert Mukherji, Deborah Abou-Kheir, Wassim Front Oncol Oncology Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key step in the invasion and malignant progression of PCa. We sought to assess the co-expression of epithelial cytokeratin 8 (CK8) and mesenchymal vimentin (Vim) in locally-advanced PCa as indicators of EMT and consequently predictors of the progression status of the disease. Methods: Co-expression of CK8 and Vim was evaluated by immunofluorescence (IF) on paraffin-embedded tissue sections of 122 patients with PCa who underwent radical prostatectomies between 1998 and 2016 at the American University of Beirut Medical Center (AUBMC). EMT score was calculated accordingly and then correlated with the patients' clinicopathological parameters and PSA failure. Results: The co-expression of CK8/Vim (EMT score), was associated with increasing Gleason group. A highly significant linear association was detected wherein higher Gleason group was associated with higher mean EMT score. In addition, the median estimated biochemical recurrence-free survival for patients with < 25% EMT score was almost double that of patients with more than 25%. The validity of this score for prediction of prognosis was further demonstrated using cox regression model. Our data also confirmed that the EMT score can predict PSA failure irrespective of Gleason group, pathological stage, or surgical margins. Conclusion: This study suggests that assessment of molecular markers of EMT, particularly CK8 and Vim, in radical prostatectomy specimens, in addition to conventional clinicopathological prognostic parameters, can aid in the development of a novel system for predicting the prognosis of locally-advanced PCa. Frontiers Media S.A. 2019-03-11 /pmc/articles/PMC6421270/ /pubmed/30915272 http://dx.doi.org/10.3389/fonc.2019.00131 Text en Copyright © 2019 Cheaito, Bahmad, Hadadeh, Saleh, Dagher, Hammoud, Shahait, Mrad, Nassif, Tawil, Bulbul, Khauli, Wazzan, Nasr, Shamseddine, Temraz, El-Sabban, El-Hajj, Mukherji and Abou-Kheir. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Cheaito, Katia A.
Bahmad, Hisham F.
Hadadeh, Ola
Saleh, Eman
Dagher, Christelle
Hammoud, Miza Salim
Shahait, Mohammad
Mrad, Zaki Abou
Nassif, Samer
Tawil, Ayman
Bulbul, Muhammad
Khauli, Raja
Wazzan, Wassim
Nasr, Rami
Shamseddine, Ali
Temraz, Sally
El-Sabban, Marwan E.
El-Hajj, Albert
Mukherji, Deborah
Abou-Kheir, Wassim
EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?
title EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?
title_full EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?
title_fullStr EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?
title_full_unstemmed EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?
title_short EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?
title_sort emt markers in locally-advanced prostate cancer: predicting recurrence?
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421270/
https://www.ncbi.nlm.nih.gov/pubmed/30915272
http://dx.doi.org/10.3389/fonc.2019.00131
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