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2. European Epidemiology of Pleural Mesothelioma—Real-Life Data From a Joint Analysis of the Mesoscape Database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma Database

Author

Stahel, Rolf, Hiltbrunner, Anita, Kammler, Rosita, Marti, Nesa, 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, Vrugt, Bart, Friess, Martina, Matter, Alessandra, Spichiger-Häusermann, Chloé, Kirschner, Michaela B., Felley-Bosco, Emanuela, Baas, Paul, Monkhorst, Kim, Nackaerts, Kristiaan, Verbeken, Eric, Weynand, Birgit, Nafteux, Philippe, Moons, Johnny, Peeters, Liesbet, Ampollini, Luca, Tiseo, Marcello, Silini, Enrico Maria, Gnetti, Letizia, Carbognani, Paolo, de Perrot, Marc, Bavaghar-Zaeimi, Fatemeh, Brcic, Luka, Samarzija, Miroslav, Seiwerth, Sven, Jakopovic, Marko, Nadal, Ernest, Cardenal, Felipe, Llatjos, Roger, Lorente, Susana, Syrigos, Konstantinos, Vamvakaris, Ioannis, Tsimpoukis, Sotirios, Boura, Paraskevi, Gray, Steven G., Finn, Stephen P., Nur, Mutaz Mohammed, Baird, Anne-Marie, Barr, Martin P., Cuffe, Sinead, Gately, Kathy, Aerts, Joachim, Thüsen, Jan von der, Bille, Andrea, Passani, Stefano, Brunelli, Alessandro, Curioni-Fontecedro, Alessandra, von der Thüsen, Jan, Kammler, Roswitha, Peters, Solange, Stahel, Rolf A., and Falcoz, Pierre-Emmanuel

Published
2023
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3. 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, and Opitz, Isabelle

Published
2022
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4. Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project.

Author

Haberecker, Martina, Rüschoff, Jan H., Andriakopoulou, Charitini, Gray, Steven G., Nackaerts, Kristiaan, De Perrot, Marc, Brcic, Luka, Nadal, Ernest, Tsimpoukis, Sotirios, Ampollini, Luca, Aerts, Joachim G., Kirschner, Michaela B., Monkhorst, Kim, Weynand, Birgit, Bavaghar-Zaeimi, Fatemeh, Samarzija, Miroslav, Llatjos, Roger, Finn, Stephen P., Silini, Enrico, and Von Der Thüsen, Jan

Subjects
IMMUNOTHERAPY, TISSUE arrays, PLEURA cancer, PROGRAMMED death-ligand 1, T cells, PROGNOSIS, CD47 antigen, MEDICAL research
Abstract

PURPOSE: CD276 (B7-H3) is an immunoregulatory protein that plays an important role in the inhibition of T-cell function. CD276 is overexpressed on a variety of human solid cancer cells with limited expression in normal tissues, making it an appealing target for innovative cancer immunotherapy approaches. Pleural mesothelioma (PM) is a highly aggressive disease with a need for new treatment options. Our objective was to investigate the expression of CD276 in the multicenter PM cohort of the European Thoracic Oncology Platform Mesoscape project and correlate the results with annotated clinical data. MATERIALS AND METHODS: Using tissue microarrays (TMAs), the expression of CD276, assessed using a semiquantitative aggregate H -score method on the membrane (and secondarily in the cytoplasm), was correlated with clinicopathologic characteristics and survival outcome. RESULTS: CD276 immunohistochemistry results were available for 353 patients, with mostly epithelioid histology (71%). Membranous CD276 expression was present in 86%. High membranous CD276 expression (H -score ≥the median H -score of 120) was significantly more common in females (P =.0029; 71% v 47%) and in epithelioid histology (P <.001; 59% v 29%), whereas no significant association in clinical outcome (overall survival [OS]/progression-free survival) was found. Cross-validation of the TMA method using whole sections revealed a moderate agreement for membranous assessment (Cohen's kappa = 0.47) and a lower agreement for cytoplasm assessment (Cohen's kappa = 0.37). In an exploratory analysis, high cytoplasmic CD276 expression was associated with worse prognosis (OS, log-rank P =.043), but was not significant when adjusting for other clinical variables. CONCLUSION: Although no prognostic value of CD276 expression was found, its high membranous expression (86%) in the PM samples of the study supports further research of its potential as a therapeutic target for this disease. [ABSTRACT FROM AUTHOR]

Published
2025
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7. Correction to: 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, and Opitz, Isabelle

Published
2022
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8. European Epidemiology of Pleural Mesothelioma—Real-Life Data From a Joint Analysis of the Mesoscape Database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma Database

Author

Opitz, Isabelle, primary, Bille, Andrea, additional, Dafni, Urania, additional, Nackaerts, Kristiaan, additional, Ampollini, Luca, additional, de Perrot, Marc, additional, Brcic, Luka, additional, Nadal, Ernest, additional, Syrigos, Konstantinos, additional, Gray, Steven G., additional, Aerts, Joachim, additional, Curioni-Fontecedro, Alessandra, additional, Rüschoff, Jan H., additional, Monkhorst, Kim, additional, Weynand, Birgit, additional, Silini, Enrico Maria, additional, Bavaghar-Zaeimi, Fatemeh, additional, Jakopovic, Marko, additional, Llatjos, Roger, additional, Tsimpoukis, Sotirios, additional, Finn, Stephen P., additional, von der Thüsen, Jan, additional, Marti, Nesa, additional, Dimopoulou, Georgia, additional, Kammler, Roswitha, additional, Peters, Solange, additional, Stahel, Rolf A., additional, Falcoz, Pierre-Emmanuel, additional, Brunelli, Alessandro, additional, Baas, Paul, additional, Stahel, Rolf, additional, Hiltbrunner, Anita, additional, Kammler, Rosita, additional, Ruepp, Barbara, additional, Tsourti, Zoi, additional, Zygoura, Panagiota, additional, Vervita, Katerina, additional, Andriakopoulou, Charitini, additional, Stavrou, Androniki, additional, Haberecker, Martina, additional, Dettwiler, Susanne, additional, Prutek, Fabiola, additional, Mittmann, Christiane, additional, Opitz, Isabelle, additional, Vrugt, Bart, additional, Friess, Martina, additional, Matter, Alessandra, additional, Spichiger-Häusermann, Chloé, additional, Kirschner, Michaela B., additional, Felley-Bosco, Emanuela, additional, Verbeken, Eric, additional, Nafteux, Philippe, additional, Moons, Johnny, additional, Peeters, Liesbet, additional, Tiseo, Marcello, additional, Gnetti, Letizia, additional, Carbognani, Paolo, additional, Samarzija, Miroslav, additional, Seiwerth, Sven, additional, Cardenal, Felipe, additional, Lorente, Susana, additional, Vamvakaris, Ioannis, additional, Boura, Paraskevi, additional, Nur, Mutaz Mohammed, additional, Baird, Anne-Marie, additional, Barr, Martin P., additional, Cuffe, Sinead, additional, Gately, Kathy, additional, Thüsen, Jan von der, additional, and Passani, Stefano, additional

Published
2023
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9. 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

Rueschoff, 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 Thusen, Jan, Marti, Nesa, Vervita, Karerina, Kammler, Roswitha, Peters, Solange, Stahel, Rolf A., Baas, Paul, Opitz, Isabelle, Rueschoff, 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 Thusen, Jan, Marti, Nesa, Vervita, Karerina, Kammler, Roswitha, Peters, Solange, Stahel, Rolf A., Baas, Paul, and Opitz, Isabelle

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 semi-quantitatively 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-naïve 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 non-epithelioid (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.

Published
2022

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