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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

Authors:
Jan Hendrik Rüschoff
Jan Hendrik Rüschoff
Jan Hendrik Rüschoff
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Martina Haberecker at University Hospital Zürich
Martina Haberecker
Zoi Tsourti at Frontier Science Foundation Hellas
Zoi Tsourti
  • Frontier Science Foundation Hellas
Kristiaan Nackaerts
Kristiaan Nackaerts
Kristiaan Nackaerts
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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.
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CORRECTION OPEN
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
Jan Hendrik Rüschoff, Martina Haberecker , Zoi Tsourti, Kristiaan Nackaerts, Marc de Perrot, Luka Brcic , Ernest Nadal,
Sotirios Tsimpoukis, Steven G. Gray, Luca Ampollini, Joachim G. Aerts, Emanuela Felley-Bosco , Michaela B. Kirschner ,
Kim Monkhorst, Birgit Weynand , Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P. Finn, Enrico Silini, Jan von
der Thüsen , Nesa Marti, Karerina Vervita, Roswitha Kammler, Solange Peters, Rolf A. Stahel, Paul Baas, Isabelle Opitz and for the
ETOP Mesoscape consortium*
© The Author(s), under exclusive licence to United States & Canadian Academy of Pathology 2022
Modern Pathology; https://doi.org/10.1038/s41379-022-01170-z
Correction to: Modern Pathology https://doi.org/10.1038/s41379-
022-01145-0, published online 17 September 2022
The original version of this article unfortunately contained an error
in an author name. A pathologist within the consortium, Dr. Letizia
Gnetti from Parma, Italy noticed that her name was missing one
letter. In lieu of ‘Gnett’it should be ‘Gnetti’. The original article has
been corrected.
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons licence, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons licence, unless
indicated otherwise in a credit line to the material. If material is not included in
the article’s Creative Commons licence and your intended use is not permitted by
statutory regulation or exceeds the permitted use, you will need to obtain permission
directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by/4.0/.
© The Author(s), under exclusive licence to United States & Canadian Academy of
Pathology 2022
*A list of authors and their affiliations appears online.
www.nature.com/modpathol
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Prevalence and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project
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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.
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Continuous sensing of nutrients and growth factors by the mTORC1-TFEB axis
Article
Full-text available
  • Sep 2023
  • eLife
mTORC1 senses nutrients and growth factors and phosphorylates downstream targets, including the transcription factor TFEB, to coordinate metabolic supply and demand. These functions position mTORC1 as a central controller of cellular homeostasis, but the behavior of this system in individual cells has not been well characterized. Here, we provide measurements necessary to refine quantitative models for mTORC1 as a metabolic controller. We developed a series of fluorescent protein-TFEB fusions and a multiplexed immunofluorescence approach to investigate how combinations of stimuli jointly regulate mTORC1 signaling at the single-cell level. Live imaging of individual MCF10A cells confirmed that mTORC1-TFEB signaling responds continuously to individual, sequential, or simultaneous treatment with amino acids and the growth factor insulin. Under physiologically relevant concentrations of amino acids, we observe correlated fluctuations in TFEB, AMPK, and AKT signaling that indicate continuous activity adjustments to nutrient availability. Using partial least squares regression modeling, we show that these continuous gradations are connected to protein synthesis rate via a distributed network of mTORC1 effectors, providing quantitative support for the qualitative model of mTORC1 as a homeostatic controller and clarifying its functional behavior within individual cells.
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