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

Jan H Rüschoff ,Kathy Gately ,Solange Peters ,Sotirios Tsimpoukis ,Chloé Spichiger-Häusermann ,Fatemeh B Zaeimi ,Enrico Maria Silini ,Charitini Andriakopoulou ,Paraskevi Boura ,Zoi Tsourti ,Martin P Barr ,Letizia Gnett ,Kristiaan Nackaerts ,Ernest Nadal ,Katerina Vervita ,Anne‐Marie Baird ,Konstantinos Syrigos ,Steven G Gray ,Bart Vrugt ,Isabelle Opitz ,Paul Baas ,Marcello Tiseo ,Marko Jakopović ,Roger Llatjos ,Christiane Mittmann ,Sven Seiwerth ,Barbara Ruepp ,Enriqueta Felip ,Mutaz Mohammed Nur ,Nesa Marti ,Panagiota Zygoura ,Paolo Carbognani ,Ioannis Vamvakaris ,Jan Von Der Thüsen ,Luka Brčić ,Miroslav Samaržija ,Eric Verbeken ,Michaela B Kirschner ,Susanne Dettwiler ,Birgit Weynand ,Joachim Aerts ,Anita Hiltbrunner ,Urania Dafni ,Emanuela Felley-Bosco ,Roswitha Kammler ,Marc De Perrot ,Karerina Vervita ,Kim Monkhorst ,Rosita Kammler ,Susana Lorente ,Luigi Ventura ,Patrick Vagenknecht ,Birgit Weyenand ,Alessandra Matter ,Androniki Stavrou ,Emanuela Felley‐Bosco ,Fatemeh Bavaghar-Zaeimi ,Rolf A Stahel ,Martina Haberecker ,Liesbet M Peeters ,Luca Ampollini ,Georgia Dimopoulou ,Fabiola Prutek ,Sinéad Cuffe ,Martina Friess ,Stephen Finn

doi:10.1038/s41379-022-01145-0

Jan H Rüschoff , Kathy Gately + Show 64 more

Open Access

https://doi.org/10.1038/s41379-022-01145-0

Copy DOI

Journal: Modern Pathology	Publication Date: Dec 1, 2022
Citations: 2	License type: open-access

Affiliation: University Hospital of Zurich

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.

Full Text