학술논문
TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome.
Document Type
Academic Journal
Author
Perez-Rivas LG; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. Luis.Perez@med.uni-muenchen.de.; Simon J; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Albani A; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Tang S; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Roeber S; Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.; Assié G; Department of Endocrinology, Center for Rare Adrenal Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.; Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France.; Deutschbein T; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.; Medicover Oldenburg MVZ, Oldenburg, Germany.; Fassnacht M; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.; Gadelha MR; Division of Endocrinology, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.; Hermus AR; Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.; Stalla GK; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Medicover Neuroendocrinology, Munich, Germany.; Tichomirowa MA; Service d'Endocrinologie, Centre Hospitalier du Nord, Ettelbruck, Luxembourg.; Rotermund R; Department of Neurosurgery, Universitätskrankenhaus Hamburg-Eppendorf, Hamburg, Germany.; Flitsch J; Department of Neurosurgery, Universitätskrankenhaus Hamburg-Eppendorf, Hamburg, Germany.; Buchfelder M; Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.; Nasi-Kordhishti I; Department of Neurosurgery, University of Tübingen, Tübingen, Germany.; Honegger J; Department of Neurosurgery, University of Tübingen, Tübingen, Germany.; Thorsteinsdottir J; Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Saeger W; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Herms J; Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.; Reincke M; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.; Theodoropoulou M; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. marily.theodoropoulou@med.uni-muenchen.de.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
Subject
Language
English
Abstract
Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing's disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.
(© 2022. The Author(s).)
(© 2022. The Author(s).)