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Endocrine Pathology

, Volume 30, Issue 4, pp 276–284 | Cite as

Loss of BAP1 in Pheochromocytomas and Paragangliomas Seems Unrelated to Genetic Mutations

  • Valeria Maffeis
  • Rocco Cappellesso
  • Lorenzo Nicolè
  • Vincenza Guzzardo
  • Chiara Menin
  • Lisa Elefanti
  • Francesca Schiavi
  • Maria Guido
  • Ambrogio FassinaEmail author
Article

Abstract

Breast cancer–associated protein 1 (BAP1) gene is a broad-spectrum tumor suppressor. Indeed, its loss of expression, due to biallelic inactivating mutations or deletions, has been described in several types of tumors including melanoma, malignant mesothelioma, renal cell carcinoma, and others. There are so far only two reports of BAP1-mutated paraganglioma, suggesting the possible involvement of this gene in paraganglioma (PGL) and pheochromocytoma (PCC) pathogenesis. We assessed BAP1 expression by immunohistochemistry (IHC) in a cohort of 56 PCC/PGL patients (and corresponding metastases, when available). Confirmatory Sanger sequencing (exons 1–17) of BAP1 has been performed in those samples which resulted negative by IHC. BAP1 nuclear expression was lost in 2/22 (9.1%) PGLs and in 12/34 (35.3%) PCCs, five of which harboring a germline mutation predisposing the development of such tumors (MENIN, MAX, SDHB, SDHD, and RET gene). Confirmatory Sanger sequencing revealed the wild-type BAP1 status of all the analyzed samples. No heterogeneity between primary and metastatic tissue was observed. This study documents that the loss of BAP1 nuclear expression is quite a frequent finding in PCC/PGL, suggesting a possible role of BAP1 in the pathogenesis of these tumors. Gene mutations do not seem to be involved in this loss of expression, at least in most cases. Other genetic and epigenetic mechanisms need to be further investigated.

Keywords

BAP1 Immunohistochemistry Sanger sequencing Pheochromocytoma Paraganglioma 

Notes

Acknowledgments

The preliminary results of this study were presented at the 29th European Congress of Pathology that was held in Amsterdam, Netherland, on the 3th of September 2017. The authors are grateful to Simone Zorzi and Mattia Pegoraro for their technical assistance.

Authors’ contributions

VM and RC: conception and design of the study, acquisition, analysis and interpretation of data, writing and revision of the manuscript. LN: acquisition and analysis of data. VG: development of methodology, technical and material contribution. CM and LE: development of methodology, technical and material contribution, revision of the manuscript. FS: collection of data. MG: reagents, material, and analysis tool contribution. AF: conception and design of the study, revision of the manuscript, supervision of the study. All of the authors confirm that each of them qualifies for all the criteria of authorship.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Valeria Maffeis
    • 1
  • Rocco Cappellesso
    • 2
  • Lorenzo Nicolè
    • 1
  • Vincenza Guzzardo
    • 1
  • Chiara Menin
    • 3
  • Lisa Elefanti
    • 3
  • Francesca Schiavi
    • 4
  • Maria Guido
    • 1
  • Ambrogio Fassina
    • 1
    Email author
  1. 1.Department of Medicine (DIMED), Surgical Pathology & Cytopathology UnitUniversity of PadovaPadovaItaly
  2. 2.Pathological Anatomy UnitPadova University HospitalPadovaItaly
  3. 3.Immunology and Molecular Oncology UnitVeneto Institute of Oncology, IOV-IRCCSPadovaItaly
  4. 4.Familial Cancer Clinic and OncoendocrinologyVeneto Institute of Oncology, IOV-IRCCSPadovaItaly

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