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One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy

Malignant pleural mesothelioma (MPM) is a mainly asbestos-related tumour associated with a very poor prognosis. Therapeutic approaches include multimodal therapy and chemotherapeutics, with cisplatin being the drug of choice, but response rates of only up to 14% indicate very poor outcomes. Effectiv...

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Autores principales: Hager, Thomas, Borchert, Sabrina, Wessolly, Michael, Mathilakathu, Alexander, Mairinger, Elena, Kollmeier, Jens, Mairinger, Thomas, Hegedus, Balazs, Greimelmaier, Kristina, Wohlschlaeger, Jeremias, Herrmann, Ken, Mairinger, Fabian Dominik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094643/
https://www.ncbi.nlm.nih.gov/pubmed/37047331
http://dx.doi.org/10.3390/ijms24076356
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author Hager, Thomas
Borchert, Sabrina
Wessolly, Michael
Mathilakathu, Alexander
Mairinger, Elena
Kollmeier, Jens
Mairinger, Thomas
Hegedus, Balazs
Greimelmaier, Kristina
Wohlschlaeger, Jeremias
Herrmann, Ken
Mairinger, Fabian Dominik
author_facet Hager, Thomas
Borchert, Sabrina
Wessolly, Michael
Mathilakathu, Alexander
Mairinger, Elena
Kollmeier, Jens
Mairinger, Thomas
Hegedus, Balazs
Greimelmaier, Kristina
Wohlschlaeger, Jeremias
Herrmann, Ken
Mairinger, Fabian Dominik
author_sort Hager, Thomas
collection PubMed
description Malignant pleural mesothelioma (MPM) is a mainly asbestos-related tumour associated with a very poor prognosis. Therapeutic approaches include multimodal therapy and chemotherapeutics, with cisplatin being the drug of choice, but response rates of only up to 14% indicate very poor outcomes. Effective treatment options are lacking. Besides the diagnostic usage of radioligands in positron emission tomography (PET)/computed tomography (CT), the endo-radioligand therapy with Lu177 has been proven as a powerful tool in cancer therapy. Mesothelin (MSLN) and C-XC chemokine receptor 4 (CXCR4) are membrane-bound proteins, expressed in certain cancers, and thus are promising targets for endo-radiotherapy. A significant portion of high MSLN- or CXCR4-expressing tumors within the MPM may open the field for this sophisticated treatment approach in the near future. Formalin-fixed, paraffin-embedded (FFPE) tumour specimens from 105 patients suffering from MPM and treated at the Lung Cancer Centre of Essen and at the Helios Klinikum Emil von Behring Berlin were screened. The tumour samples were arranged in tissue microarrays. We immunohistochemically stained the tumour samples against MSLN and CXCR4. The protein expressions of the stainings were scored by a pathologist by using a semiquantitative method. The data obtained were correlated with the clinical outcome. Overall, 77.1% of the analysed tumours showed CXCR4 protein expression (25.7% of them at high expression level (Score 3)). 48.6% of all samples showed an overall strong staining (Score ≥ 2), 59% of the investigated tumours showed MSLN protein expression (10.5% of them at high expression (Score 3)), and 36.2% of all samples showed an overall strong staining (Score ≥ 2). Our results show significant tissue expression levels, for both CXCR4 and MSLN protein, in a major portion of clinical MPM samples. One-third of patients showed outstanding immunoexpression of at least one of these markers, making them interesting candidates for radioligand-based PET/CT diagnostics and follow-up and furthermore may profit from endo-radiotherapy.
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spelling pubmed-100946432023-04-13 One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy Hager, Thomas Borchert, Sabrina Wessolly, Michael Mathilakathu, Alexander Mairinger, Elena Kollmeier, Jens Mairinger, Thomas Hegedus, Balazs Greimelmaier, Kristina Wohlschlaeger, Jeremias Herrmann, Ken Mairinger, Fabian Dominik Int J Mol Sci Article Malignant pleural mesothelioma (MPM) is a mainly asbestos-related tumour associated with a very poor prognosis. Therapeutic approaches include multimodal therapy and chemotherapeutics, with cisplatin being the drug of choice, but response rates of only up to 14% indicate very poor outcomes. Effective treatment options are lacking. Besides the diagnostic usage of radioligands in positron emission tomography (PET)/computed tomography (CT), the endo-radioligand therapy with Lu177 has been proven as a powerful tool in cancer therapy. Mesothelin (MSLN) and C-XC chemokine receptor 4 (CXCR4) are membrane-bound proteins, expressed in certain cancers, and thus are promising targets for endo-radiotherapy. A significant portion of high MSLN- or CXCR4-expressing tumors within the MPM may open the field for this sophisticated treatment approach in the near future. Formalin-fixed, paraffin-embedded (FFPE) tumour specimens from 105 patients suffering from MPM and treated at the Lung Cancer Centre of Essen and at the Helios Klinikum Emil von Behring Berlin were screened. The tumour samples were arranged in tissue microarrays. We immunohistochemically stained the tumour samples against MSLN and CXCR4. The protein expressions of the stainings were scored by a pathologist by using a semiquantitative method. The data obtained were correlated with the clinical outcome. Overall, 77.1% of the analysed tumours showed CXCR4 protein expression (25.7% of them at high expression level (Score 3)). 48.6% of all samples showed an overall strong staining (Score ≥ 2), 59% of the investigated tumours showed MSLN protein expression (10.5% of them at high expression (Score 3)), and 36.2% of all samples showed an overall strong staining (Score ≥ 2). Our results show significant tissue expression levels, for both CXCR4 and MSLN protein, in a major portion of clinical MPM samples. One-third of patients showed outstanding immunoexpression of at least one of these markers, making them interesting candidates for radioligand-based PET/CT diagnostics and follow-up and furthermore may profit from endo-radiotherapy. MDPI 2023-03-28 /pmc/articles/PMC10094643/ /pubmed/37047331 http://dx.doi.org/10.3390/ijms24076356 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hager, Thomas
Borchert, Sabrina
Wessolly, Michael
Mathilakathu, Alexander
Mairinger, Elena
Kollmeier, Jens
Mairinger, Thomas
Hegedus, Balazs
Greimelmaier, Kristina
Wohlschlaeger, Jeremias
Herrmann, Ken
Mairinger, Fabian Dominik
One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy
title One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy
title_full One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy
title_fullStr One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy
title_full_unstemmed One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy
title_short One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy
title_sort one third of malignant pleural mesothelioma shows high immunohistochemical expression of msln or cxcr4 which indicates potent candidates for endo-radiotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094643/
https://www.ncbi.nlm.nih.gov/pubmed/37047331
http://dx.doi.org/10.3390/ijms24076356
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