Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec;35(12):1888-1899.
doi: 10.1038/s41379-022-01145-0. Epub 2022 Sep 17.

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  1 , Martina Haberecker  1 , Zoi Tsourti  2 , Kristiaan Nackaerts  3 , Marc de Perrot  4 , Luka Brcic  5 , Ernest Nadal  6 , Sotirios Tsimpoukis  7 , Steven G Gray  8 , Luca Ampollini  9 , Joachim G Aerts  10 , Emanuela Felley-Bosco  11 , Michaela B Kirschner  11 , Kim Monkhorst  12 , Birgit Weynand  13 , Fatemeh Bavaghar-Zaeimi  14 , Miroslav Samarzija  15 , Roger Llatjos  16 , Stephen P Finn  17 , Enrico Silini  9 , Jan von der Thüsen  18 , Nesa Marti  19 , Karerina Vervita  2 , Roswitha Kammler  19 , Solange Peters  20 , Rolf A Stahel  21 , Paul Baas  22 , Isabelle Opitz  23 ; ETOP Mesoscape consortium
Collaborators, Affiliations

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 et al. Mod Pathol. 2022 Dec.

Erratum in

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.

PubMed Disclaimer

Conflict of interest statement

JHR, MH, ZT, KN, MDP, ST, SGG, LA, EFB, MBK, KM, BW, FBZ, MS, RL, SPF, ES, NM, RK, RAS declared no conflict of interest. EN declares his participation in the following advisoriy boards and lectures: Roche, BMS, MSD, Merck-Serono, Pfizer, Lilly, Amgen, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi and Bayer and his research support from: Roche, Pfizer, Merck-Serono and BMS. JA declares: Adv board BMS, Eli-Lilly, MSD, Bayer, Amphera, Roche/Stock owner Amphera/Patent on allogenic tumor lysate, combination immunotherapy. JVDT declares: Adv board and lectures: AstraZeneca, BMS, Eli-Lilly, Johnson&Johnson, MSD, Pfizer, Roche. SP delclares: I have received education grants, provided consultation, attended advisory boards and/or provided lectures for the following organizations, from whom I have received honoraria (all fees to institution): Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda.Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda.Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics, Roche/Genentech. PB declares: Consultancy roel for BMS, Advisory Board for MSD, Beigene, Pfizer, Takeda and Boehringer Ingelheim. Research Grants from AZ and BMS. IO declares: Consultation / Advisory role: AstraZeneca, Bristol-Myers Squibb, MSD Merck Sharp & Dohme AG. Talk in a company’s organized public event: AstraZeneca, Roche. Receipt of grants/research supports: Institutional grants for fellowships from Medtronic, Roche. Proctorship for Intuitive.

Figures

Fig. 1
Fig. 1. Immunohistochemical staining of pS6 ribosomal protein in pleural mesothelioma (PM).
A Hematoxylin and eosin stained TMA punches of epithelioid PM and corresponding immunohistochemical pS6 ribosomal protein staining. The immunohistochemical staining intensity reaching from 1 (weak), 2 (moderate) to 3 (strong). B Hematoxylin and eosin stained TMA punches of sarcomatoid PM and corresponding immunohistochemical pS6 ribosomal protein staining. TMA tissue micro array, PM pleural mesothelioma. Scale bar 200 µm.
Fig. 2
Fig. 2. Distribution of H-scores.
Grey vertical line represents the median value of H-scores.
Fig. 3
Fig. 3. Bar plot of pS6 high prevalence by subgroups of interest.
*Category “Both” is excluded. All p-values refer to Fisher’s exact test.
Fig. 4
Fig. 4. Overall survival (OS) according to histological subtype.
A OS by pS6 status; epithelioid patients. B OS by pS6 status; non-epithelioid patients. Interaction p-value (from Cox model including pS6 status with histology interaction): <0.001. Overall median OS was 23.1 months (95% CI: 19.9–25.2) for epithelioid patients and 13.7 months (95% CI: 10.7–15.7) for non-epithelioid. Log-rank p-value comparing pS6 high vs. low: 0.88 for epithelioid; <0.001 for non-epithelioid.
Fig. 5
Fig. 5. Progression-free survival (PFS) by pS6 status and histological subtype.
A PFS by pS6 status; epithelioid patients. B PFS by pS6 status; non-epithelioid patients. Interaction p-value (from Cox model including pS6 status with histology interaction): <0.001. Overall median PFS was 14.3 months (95% CI: 12.4–15.9) for epithelioid patients and 8.8 months (95% CI: 6.3–10.4) for non-epithelioid. Log-rank p-value comparing pS6 high vs. low: 0.18 for epithelioid; <0.001 for non-epithelioid.
See this image and copyright information in PMC

References

    1. Carbone M, Adusumilli PS, Alexander HR, Baas P, Bardelli F, Bononi A, et al. Mesothelioma: Scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin 69, 402–429 (2019) - PMC - PubMed
    1. Taioli E, Wolf AS, Camacho-Rivera M, Kaufman A, Lee DS, Nicastr D, et al. Determinants of survival in malignant pleural mesothelioma: a surveillance, epidemiology, and end results (SEER) study of 14,228 patients. PLoS One 10 (2015) - PMC - PubMed
    1. Tolani B, Acevedo LA, Hoang NT, Biao H. Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications. Int J Mol Sci 19 (2018) - PMC - PubMed
    1. Carbone M, Kratzke RA, Testa JR. The pathogenesis of mesothelioma. Sem Oncol 29, 2–17 (2002) - PubMed
    1. Flores RM, Zakowski M, Venkatraman E, Krug L, Rosenzweig K, Dycoco J, et al. Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center. J Thorac Oncol 2, 957–965 2007) - PubMed

Publication types

Substances