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BAP1 Protein is a Progression Factor in Malignant Pleural Mesothelioma

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Pathology & Oncology Research

Abstract

Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time - the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.

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Acknowledgments

The study was partly supported by an unrestricted grant from Pfizer Austria.

We gratefully thank Hildegard Gleixner, Margit Gogg-Kamerer, Elisabeth Grygar and Mohammed Al-Effah, Institute of Pathology, Medical University of Graz, for excellent technical assistance.

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Authors and Affiliations

  1. Institute of Pathology, Research Unit for Molecular Lung- and Pleura Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036, Graz, Austria

    Lisa Arzt, Iris Halbwedl & Helmut H. Popper

  2. Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2/V, 8036, Graz, Austria

    Franz Quehenberger

  3. Institute of Pathology, Helios Klinikum Berlin, Walterhöferstraße 11, 14156, Berlin, Germany

    Thomas Mairinger

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  1. Lisa Arzt
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  2. Franz Quehenberger
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Correspondence to Lisa Arzt.

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Lisa Arzt and Franz Quehenberger contributed equally to the study.

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Arzt, L., Quehenberger, F., Halbwedl, I. et al. BAP1 Protein is a Progression Factor in Malignant Pleural Mesothelioma. Pathol. Oncol. Res. 20, 145–151 (2014). https://doi.org/10.1007/s12253-013-9677-2

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