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http://hdl.handle.net/2445/196114
Title: | Expression of phosphorylated ribosomal protein S6 in mesothelioma patients - correlation with clinico-pathological characteristics and outcome: results from the European Thoracic Oncology Platform (ETOP) Mesoscape project |
Author: | Rüschoff, Jan Hendrik Haberecker, Martina Tsourti, Zoi Nackaerts, Kristiaan De Perrot, Marc Brcic, Luka Nadal, Ernest Tsimpoukis, Sotirios Gray, Steven G. Ampollini, Luca Aerts, Joachim G. Felley Bosco, Emanuela Kirschner, Michaela B. Monkhorst, Kim Weynand, Birgit Bavaghar Zaeimi, Fatemeh Samarzija, Miroslav Llatjos, Roger Finn, Stephen P. Silini, Enrico Von Der Thüsen, Jan Marti, Nesa Vervita, Karerina Kammler, Roswitha Peters, Solange Stahel, Rolf A. Baas, Paul Opitz, Isabelle Stahel, Rolf Hiltbrunner, Anita Kammler, Rosita Marti, Nesa Vagenknecht, Patrick Ruepp, Barbara Dafni, Urania Tsourti, Zoi Zygoura, Panagiota Vervita, Katerina Dimopoulou, Georgia Andriakopoulou, Charitini Stavrou, Androniki Rüschoff, Jan H. Haberecker, Martina Dettwiler, Susanne Prutek, Fabiola Mittmann, Christiane Opitz, Isabelle Baas, Paul Opitz, Isabelle Vrugt, Bart Friess, Martina Matter, Alessandra Spichiger Häusermann, Chloé Baas, Paul Verbeken, Eric Weyenand, Birgit Peeters, Liesbet Tiseo, Marcello Silini, Enrico Maria Ventura, Luigi Gnetti, Letizia Carbognani, Paolo Zaeimi, Fatemeh B. Seiwerth, Sven Jakopovic, Marko Cardenal, Felipe Lorente, Susana Syrigos, Konstantinos Vamvakaris, Ioannis Boura, Paraskevi Gray, Steven Nur, Mutaz Mohammed Baird, Anne Marie Barr, Martin Cuffe, Sinead Gately, Kathy ETOP Mesoscape consortium |
Keywords: | Càncer de pulmó Mesotelioma Pleura Pronòstic mèdic Lung cancer Mesothelioma Pleura Prognosis |
Issue Date: | 1-Dec-2022 |
Publisher: | Elsevier BV |
Abstract: | Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation. In previous studies, low phosphorylated S6 (pS6) immunoreactivity was significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. We aimed to correlate pS6 expression to clinical data in a large multi-centre PM cohort as part of the European Thoracic Oncology Platform (ETOP) Mesoscape project. Tissue Micro Arrays (TMAs) of PM were constructed and expression of pS6 was evaluated by a semiquantitatively aggregate H-score. Expression results were correlated to patient characteristics as well as OS/PFS. pS6 IHC results of 364 patients from 9 centres, diagnosed between 1999 and 2017 were available. The primary histology of included tumours was epithelioid (70.3%), followed by biphasic (24.2%) and sarcomatoid (5.5%). TMAs included both treatment-naive and tumour tissue taken after induction chemotherapy. High pS6 expression (181 patients with H-score>1.41) was significantly associated with less complete resection. In the overall cohort, OS/PFS were not significantly different between pS6-low and pS6-high patients. In a subgroup analysis nonepithelioid (biphasic and sarcomatoid) patients with high pS6 expression showed a significantly shorter OS (p< 0.001, 10.7 versus 16.9 months) and PFS (p < 0.001, 6.2 versus 10.8 months). In subgroup analysis, in non-epithelioid PM patients high pS6 expression was associated with significantly shorter OS and PFS. These exploratory findings suggest a clinically relevant PI3K pathway activation in non-epithelioid PM which might lay the foundation for future targeted treatment strategies. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41379-022-01145-0 |
It is part of: | Modern Pathology, 2022, vol. 35, num. 12, p. 1888-1899 |
URI: | http://hdl.handle.net/2445/196114 |
Related resource: | https://doi.org/10.1038/s41379-022-01145-0 |
ISSN: | 0893-3952 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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