PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy
| Autor: | Walter Weder, Rolf A. Stahel, Alex Soltermann, Svenja Thies, Mayura Meerang, Byron K.Y. Bitanihirwe, Holger Moch, Ghassan Allo, Emanuela Felley-Bosco, Marc de Perrot, Martina Friess, Isabelle Opitz, Lukas Frischknecht, Ming-Sound Tsao, Burkhardt Seifert |
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| Přispěvatelé: | University of Zurich, Opitz, Isabelle |
| Rok vydání: | 2014 |
| Předmět: |
Male
Mesothelioma Pathology 10255 Clinic for Thoracic Surgery Deoxycytidine Cohort Studies Immunoenzyme Techniques Glutamates Antineoplastic Combined Chemotherapy Protocols Medicine Pneumonectomy In Situ Hybridization Fluorescence Tissue microarray biology TOR Serine-Threonine Kinases Remission Induction Induction Chemotherapy Middle Aged Prognosis Combined Modality Therapy 3. Good health Survival Rate Pemetrexed Oncology Multimodality treatment Ki-67 2730 Oncology Female medicine.drug Signal Transduction Pulmonary and Respiratory Medicine Adult medicine.medical_specialty Guanine Phosphatase and tensin homologue Pleural Neoplasms 610 Medicine & health 10049 Institute of Pathology and Molecular Pathology Biomarkers Tumor PTEN Humans Phosphatidylinositol 3-kinase/mammalian target of rapamycin Survival rate Survival analysis PI3K/AKT/mTOR pathway Aged Neoplasm Staging business.industry PTEN Phosphohydrolase Induction chemotherapy 10060 Epidemiology Biostatistics and Prevention Institute (EBPI) medicine.disease Gemcitabine 10022 Division of Surgical Research 2740 Pulmonary and Respiratory Medicine Tissue Array Analysis 10032 Clinic for Oncology and Hematology Cancer research biology.protein Cisplatin Phosphatidylinositol 3-Kinase business Follow-Up Studies |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study o |
| DOI: | 10.1097/JTO.0000000000000055 |
| Popis: | 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 naive 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. |
| Databáze: | OpenAIRE |
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