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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
- Source :
- Rueschoff , J H , Haberecker , M , ETOP Mesoscape Consortium , Tsourti , Z , Nackaerts , K , de Perrot , M , Brcic , L , Nadal , E , Tsimpoukis , S , Gray , S G , Ampollini , L , Aerts , J G , Felley-Bosco , E , Kirschner , M B , Monkhorst , K , Weynand , B , Bavaghar-Zaeimi , F , Samarzija , M , Llatjos , R , Finn , S P , Silini , E , von der Thusen , J , Marti , N , Vervita , K , Kammler , R , Peters , S , Stahel , R A , Baas , P & Opitz , I 2022 , ' 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 ' , Modern Pathology , vol. 35 , no. 12 , pp. 1888-1899 .
- Publication Year :
- 2022
-
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-naìˆve 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.
Details
- Database :
- OAIster
- Journal :
- Rueschoff , J H , Haberecker , M , ETOP Mesoscape Consortium , Tsourti , Z , Nackaerts , K , de Perrot , M , Brcic , L , Nadal , E , Tsimpoukis , S , Gray , S G , Ampollini , L , Aerts , J G , Felley-Bosco , E , Kirschner , M B , Monkhorst , K , Weynand , B , Bavaghar-Zaeimi , F , Samarzija , M , Llatjos , R , Finn , S P , Silini , E , von der Thusen , J , Marti , N , Vervita , K , Kammler , R , Peters , S , Stahel , R A , Baas , P & Opitz , I 2022 , ' 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 ' , Modern Pathology , vol. 35 , no. 12 , pp. 1888-1899 .
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1349453181
- Document Type :
- Electronic Resource