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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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6356 |
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| author | Thomas Hager Sabrina Borchert Michael Wessolly Alexander Mathilakathu Elena Mairinger Jens Kollmeier Thomas Mairinger Balazs Hegedus Kristina Greimelmaier Jeremias Wohlschlaeger Ken Herrmann Fabian Dominik Mairinger |
| author_facet | Thomas Hager Sabrina Borchert Michael Wessolly Alexander Mathilakathu Elena Mairinger Jens Kollmeier Thomas Mairinger Balazs Hegedus Kristina Greimelmaier Jeremias Wohlschlaeger Ken Herrmann Fabian Dominik Mairinger |
| author_sort | Thomas Hager |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T05:36:05Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:05Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-af62e333fb3b4b25b1feb1a0f7945c792023-11-17T16:49:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247635610.3390/ijms24076356One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-RadiotherapyThomas Hager0Sabrina Borchert1Michael Wessolly2Alexander Mathilakathu3Elena Mairinger4Jens Kollmeier5Thomas Mairinger6Balazs Hegedus7Kristina Greimelmaier8Jeremias Wohlschlaeger9Ken Herrmann10Fabian Dominik Mairinger11Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyDepartment of Pneumology, Helios Klinikum Emil von Behring, 14165 Berlin, GermanyDepartment of Pathology, Helios Klinikum Emil von Behring, 14165 Berlin, GermanyRuhrlandklinik, West German Lung Centre, University Hospital Essen, University of Duisburg-Essen, 45239 Essen, GermanyDepartment of Pathology, Diakonissenkrankenhaus Flensburg, 24939 Flensburg, GermanyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyClinic for Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyMalignant 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.https://www.mdpi.com/1422-0067/24/7/6356pleural mesotheliomabiomarkersCXCR4MSLNradioligandendo-radiotherapy |
| spellingShingle | Thomas Hager Sabrina Borchert Michael Wessolly Alexander Mathilakathu Elena Mairinger Jens Kollmeier Thomas Mairinger Balazs Hegedus Kristina Greimelmaier Jeremias Wohlschlaeger Ken Herrmann Fabian Dominik Mairinger One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy International Journal of Molecular Sciences pleural mesothelioma biomarkers CXCR4 MSLN radioligand 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 | pleural mesothelioma biomarkers CXCR4 MSLN radioligand endo-radiotherapy |
| url | https://www.mdpi.com/1422-0067/24/7/6356 |
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