PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy.

Détails

ID Serval
serval:BIB_1DCDFEFFCBAF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy.
Périodique
Journal of Thoracic Oncology
Auteur(s)
Bitanihirwe B.K., Meerang M., Friess M., Soltermann A., Frischknecht L., Thies S., Felley-Bosco E., Tsao M.S., Allo G., de Perrot M., Seifert B., Moch H., Stahel R., Weder W., Opitz I.
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
9
Numéro
2
Pages
239-247
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
INTRODUCTION: The prognostic significance of activity biomarkers within the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway was assessed in two independent cohorts of malignant pleural mesothelioma (MPM) patients uniformly treated with a multimodal approach. We specifically assessed expression signatures in a unique set of pre- and postchemotherapy tumor samples.
METHODS: Biomarker expression was assessed in samples of two independent cohorts of 107 (cohort 1) and 46 (cohort 2) MPM cases uniformly treated with platinum-based induction chemotherapy followed by extrapleural pneumonectomy from two different institutions, assembled on tissue microarrays. Expression levels of phosphatase and tensin homologue (PTEN), phospho-mTOR, and p-S6 in addition to marker of proliferation (Ki-67) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry and correlated with overall survival (OAS) and progression-free survival (PFS). To assess PTEN genomic status, fluorescence in situ hybridization was performed.
RESULTS: Survival analysis showed that high p-S6 and Ki-67 expression in samples of treatment naïve patients of cohort 1 was associated with shorter PFS (p = 0.02 and p = 0.04, respectively). High Ki-67 expression after chemotherapy remained associated with shorter PFS (p = 0.03) and OAS (p = 0.02). Paired comparison of marker expression in samples before and after induction chemotherapy of cohort 1 revealed that decreased cytoplasmic PTEN and increased phospho-mTOR expression was associated with a worse OAS (p = 0.04 and p = 0.03, respectively).
CONCLUSIONS: These novel data reveal a prognostic significance of expression changes of PI3K/mTOR pathway components during induction chemotherapy if confirmed in other patient cohorts and support the growing evidence to target the PI3K/mTOR pathway in the treatment of MPM.
Mots-clé
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/metabolism, Cisplatin/administration & dosage, Cohort Studies, Combined Modality Therapy, Deoxycytidine/administration & dosage, Deoxycytidine/analogs & derivatives, Female, Follow-Up Studies, Glutamates/administration & dosage, Guanine/administration & dosage, Guanine/analogs & derivatives, Humans, Immunoenzyme Techniques, In Situ Hybridization, Fluorescence, Induction Chemotherapy, Male, Mesothelioma/metabolism, Mesothelioma/pathology, Middle Aged, Neoplasm Staging, PTEN Phosphohydrolase/genetics, PTEN Phosphohydrolase/metabolism, Pemetrexed, Phosphatidylinositol 3-Kinase/metabolism, Pleural Neoplasms/metabolism, Pleural Neoplasms/pathology, Pneumonectomy, Prognosis, Remission Induction, Signal Transduction, Survival Rate, TOR Serine-Threonine Kinases/metabolism, Tissue Array Analysis
Pubmed
Web of science
Création de la notice
03/08/2014 14:31
Dernière modification de la notice
03/03/2018 14:34
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