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MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic b...

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Autores principales: Pasello, Giulia, Urso, Loredana, Mencoboni, Manlio, Grosso, Federica, Ceresoli, Giovanni Luca, Lunardi, Francesca, Vuljan, Stefania Edith, Bertorelle, Roberta, Sacchetto, Valeria, Ciminale, Vincenzo, Rea, Federico, Favaretto, Adolfo, Conte, PierFranco, Calabrese, Fiorella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747209/
https://www.ncbi.nlm.nih.gov/pubmed/26544728
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author Pasello, Giulia
Urso, Loredana
Mencoboni, Manlio
Grosso, Federica
Ceresoli, Giovanni Luca
Lunardi, Francesca
Vuljan, Stefania Edith
Bertorelle, Roberta
Sacchetto, Valeria
Ciminale, Vincenzo
Rea, Federico
Favaretto, Adolfo
Conte, PierFranco
Calabrese, Fiorella
author_facet Pasello, Giulia
Urso, Loredana
Mencoboni, Manlio
Grosso, Federica
Ceresoli, Giovanni Luca
Lunardi, Francesca
Vuljan, Stefania Edith
Bertorelle, Roberta
Sacchetto, Valeria
Ciminale, Vincenzo
Rea, Federico
Favaretto, Adolfo
Conte, PierFranco
Calabrese, Fiorella
author_sort Pasello, Giulia
collection PubMed
description Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p < 0.001), HIF1alpha (p = 0.013), necrosis (p = 0.013) and proliferation index (p < 0.001) were seen mainly in sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features.
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spelling pubmed-47472092016-03-25 MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data Pasello, Giulia Urso, Loredana Mencoboni, Manlio Grosso, Federica Ceresoli, Giovanni Luca Lunardi, Francesca Vuljan, Stefania Edith Bertorelle, Roberta Sacchetto, Valeria Ciminale, Vincenzo Rea, Federico Favaretto, Adolfo Conte, PierFranco Calabrese, Fiorella Oncotarget Research Paper Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p < 0.001), HIF1alpha (p = 0.013), necrosis (p = 0.013) and proliferation index (p < 0.001) were seen mainly in sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features. Impact Journals LLC 2015-10-30 /pmc/articles/PMC4747209/ /pubmed/26544728 Text en Copyright: © 2015 Pasello et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Pasello, Giulia
Urso, Loredana
Mencoboni, Manlio
Grosso, Federica
Ceresoli, Giovanni Luca
Lunardi, Francesca
Vuljan, Stefania Edith
Bertorelle, Roberta
Sacchetto, Valeria
Ciminale, Vincenzo
Rea, Federico
Favaretto, Adolfo
Conte, PierFranco
Calabrese, Fiorella
MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
title MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
title_full MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
title_fullStr MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
title_full_unstemmed MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
title_short MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
title_sort mdm2 and hif1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: correlation with pathological and clinical data
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747209/
https://www.ncbi.nlm.nih.gov/pubmed/26544728
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