Top

Head and Neck Pathology

Published in:

18-08-2023 | Case Report

Loss of BAP1 Protein Expression by Immunohistochemistry in the Salivary Duct Carcinoma Component of an Intracapsular Carcinoma ex Pleomorphic Adenoma of the Parotid Gland

Authors: Eleonora Fiorletta Quiroga, Patricia R. Connor, Lisa Rooper, Mauricio A. Moreno, J. Stephen Nix

Published in: Head and Neck Pathology | Issue 3/2023

Abstract

Background

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is altered in a variety of neoplasms as well as in BAP1 tumor predisposition syndrome. BAP1 alterations are associated with aggressive behavior in some malignancies and may have treatment implications in future. We present the first documented case of loss of BAP1 protein expression by immunohistochemistry in the salivary duct carcinoma (SDC) component of an intracapsular carcinoma ex pleomorphic adenoma (CXPA) in the context of molecular loss of function of BAP1 in the neoplasm.

Methods

A woman of approximately 55 years of age presented with a deep parotid lobe mass, which was resected and found to be CXPA. BAP1 immunohistochemistry and next-generation sequencing was performed to further characterize the neoplasm.

Results

The neoplasm showed loss of BAP1 protein expression in the SDC component but retention in the residual pleomorphic adenoma (PA). Next-generation sequencing confirmed a BAP1 loss of function alteration in the neoplasm.

Conclusion

This is the first documented case report of BAP1 protein expression loss in the SDC component of a CXPA. Future studies are needed to investigate the relevance of BAP1 alterations in SDC and CXPA, which may have prognostic and treatment implications.

Antony J, Gopalan V, Smith RA, Lam AK (2012) Carcinoma ex pleomorphic adenoma: a comprehensive review of clinical, pathological and molecular data. Head Neck Pathol 6(1):1–9. https://doi.org/10.1007/s12105-011-0281-zCrossRefPubMed

Bubola J, MacMillan CM, Demicco EG et al (2021) Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors. Genes Chromosomes Cancer 60(10):695–708. https://doi.org/10.1002/gcc.22979CrossRefPubMedPubMedCentral

Chau C, van Doorn R, van Poppelen NM et al (2019) Families with BAP1-tumor predisposition syndrome in The Netherlands: path to identification and a proposal for genetic screening guidelines. Cancers. https://doi.org/10.3390/cancers11081114CrossRefPubMedPubMedCentral

Dogan S, Ng CKY, Xu B et al (2019) The repertoire of genetic alterations in salivary duct carcinoma including a novel HNRNPH3-ALK rearrangement. Hum Pathol 88:66–77. https://doi.org/10.1016/j.humpath.2019.03.004CrossRefPubMedPubMedCentral

El Hallani S, Udager AM, Bell D et al (2018) Epithelial-myoepithelial carcinoma: frequent morphologic and molecular evidence of preexisting pleomorphic adenoma, common HRAS mutations in PLAG1-intact and HMGA2-intact cases, and occasional TP53, FBXW7, and SMARCB1 alterations in high-grade cases. Am J Surg Pathol 42(1):18–27. https://doi.org/10.1097/pas.0000000000000933CrossRefPubMedPubMedCentral

Eletr ZM, Wilkinson KD (2011) An emerging model for BAP1’s role in regulating cell cycle progression. Cell Biochem Biophys 60(1–2):3–11. https://doi.org/10.1007/s12013-011-9184-6CrossRefPubMedPubMedCentral

Eletr ZM, Yin L, Wilkinson KD (2013) BAP1 is phosphorylated at serine 592 in S-phase following DNA damage. FEBS Lett 587(24):3906–3911. https://doi.org/10.1016/j.febslet.2013.10.035CrossRefPubMedPubMedCentral

George TJ, DeRemer DL, Parekh HD et al (2020) Phase II trial of the PARP inhibitor, niraparib, in BAP1 and other DNA damage response (DDR) pathway deficient neoplasms including cholangiocarcinoma. J Clin Oncol. https://doi.org/10.1200/JCO.2020.38.4_suppl.TPS591CrossRefPubMedPubMedCentral

Griffith CC, Seethala RR, Luvison A, Miller M, Chiosea SI (2013) PIK3CA mutations and PTEN loss in salivary duct carcinomas. Am J Surg Pathol 37(8):1201–1207. https://doi.org/10.1097/PAS.0b013e3182880d5aCrossRefPubMed

10.

Griffith CC, Thompson LDR, Assaad A et al (2014) Salivary duct carcinoma and the concept of early carcinoma ex pleomorphic adenoma. Histopathology 65(6):854–860. https://doi.org/10.1111/his.12454CrossRefPubMed

11.

Harbour JW, Onken MD, Roberson ED et al (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330(6009):1410–1413. https://doi.org/10.1126/science.1194472CrossRefPubMedPubMedCentral

12.

Hassan R, Mian I, Wagner C et al (2020) Phase II study of olaparib in malignant mesothelioma (MM) to correlate efficacy with germline and somatic mutations in DNA repair genes. J Clin Oncol 38(15):9054–9054. https://doi.org/10.1200/JCO.2020.38.15_suppl.9054CrossRef

13.

Hassan R, Morrow B, Thomas A et al (2019) Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Proc Natl Acad Sci USA 116(18):9008–9013. https://doi.org/10.1073/pnas.1821510116CrossRefPubMedPubMedCentral

14.

Irani S, Bidari-Zerehpoush F (2017) BRCA1/2 mutations in salivary pleomorphic adenoma and carcinoma-ex-pleomorphic adenoma. J Int Soc Prev Community Dent 7(Suppl 3):S155-s162. https://doi.org/10.4103/jispcd.JISPCD_184_17CrossRefPubMedPubMedCentral

15.

Jensen DE, Proctor M, Marquis ST et al (1998) BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 16(9):1097–1112. https://doi.org/10.1038/sj.onc.1201861CrossRefPubMed

16.

Kakkar A, Guleria P, Madan K, Kumar R, Kumar S, Jain D (2019) Immunohistochemical assessment of BAP1 protein in mucoepidermoid carcinomas. Indian J Otolaryngol Head Neck Surg 71(1):33–37. https://doi.org/10.1007/s12070-018-1549-3CrossRefPubMed

17.

Kwon J, Lee D, Lee S-A (2023) BAP1 as a guardian of genome stability: implications in human cancer. Exp Mol Med. https://doi.org/10.1038/s12276-023-00979-1CrossRefPubMedPubMedCentral

18.

Laitman Y, Newberg J, Molho RB, Jin DX, Friedman E (2021) The spectrum of tumors harboring BAP1 gene alterations. Cancer Genet 256–257:31–35. https://doi.org/10.1016/j.cancergen.2021.03.007CrossRefPubMed

19.

Louie BH, Kurzrock R (2020) BAP1: Not just a BRCA1-associated protein. Cancer Treat Rev 90:102091. https://doi.org/10.1016/j.ctrv.2020.102091CrossRefPubMedPubMedCentral

20.

Masoomian B, Shields JA, Shields CL (2018) Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. J Curr Ophthalmol 30(2):102–109. https://doi.org/10.1016/j.joco.2018.02.005CrossRefPubMedPubMedCentral

21.

Nakajima Y, Kishimoto T, Nagai Y et al (2009) Expressions of androgen receptor and its co-regulators in carcinoma ex pleomorphic adenoma of salivary gland. Pathology 41(7):634–639. https://doi.org/10.3109/00313020903071595CrossRefPubMed

22.

Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH (2016) Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet 89(3):285–294. https://doi.org/10.1111/cge.12630CrossRefPubMed

23.

Santana T, Pavel A, Martinek P et al (2019) Biomarker immunoprofile and molecular characteristics in salivary duct carcinoma: clinicopathological and prognostic implications. Hum Pathol 93:37–47. https://doi.org/10.1016/j.humpath.2019.08.009CrossRefPubMed

24.

Shankar GM, Santagata S (2017) BAP1 mutations in high-grade meningioma: implications for patient care. Neuro Oncol 19(11):1447–1456. https://doi.org/10.1093/neuonc/nox094CrossRefPubMedPubMedCentral

25.

Tondi-Resta I, Hobday SB, Gubbiotti MA et al (2023) Carcinoma ex pleomorphic adenomas: an institutional experience and literature review. Am J Clin Pathol. https://doi.org/10.1093/ajcp/aqac181CrossRefPubMed

26.

Wang K, McDermott JD, Schrock AB et al (2017) Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations. Ann Oncol 28(4):748–753. https://doi.org/10.1093/annonc/mdw689CrossRefPubMed

27.

Wang K, Russell JS, McDermott JD et al (2016) Profiling of 149 salivary duct carcinomas, carcinoma ex pleomorphic adenomas, and adenocarcinomas, not otherwise specified reveals actionable genomic alterations. Clin Cancer Res 22(24):6061–6068. https://doi.org/10.1158/1078-0432.CCR-15-2568CrossRefPubMed

28.

Yu H, Pak H, Hammond-Martel I et al (2014) Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci USA 111(1):285–290. https://doi.org/10.1073/pnas.1309085110CrossRefPubMed

Title: Loss of BAP1 Protein Expression by Immunohistochemistry in the Salivary Duct Carcinoma Component of an Intracapsular Carcinoma ex Pleomorphic Adenoma of the Parotid Gland
Authors: Eleonora Fiorletta Quiroga
Patricia R. Connor
Lisa Rooper
Mauricio A. Moreno
J. Stephen Nix
Publication date: 18-08-2023
Publisher: Springer US
Published in: Head and Neck Pathology / Issue 3/2023
Electronic ISSN: 1936-0568
DOI: https://doi.org/10.1007/s12105-023-01579-1

At a glance: The STEP trials

Springer Medicine

Loss of BAP1 Protein Expression by Immunohistochemistry in the Salivary Duct Carcinoma Component of an Intracapsular Carcinoma ex Pleomorphic Adenoma of the Parotid Gland

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2023

Atypical Squamous Verrucous Lesions of the Oral Cavity: Challenges in Interpretation of Small Incisional Biopsies

Low-Grade Myofibroblastic Sarcoma of the Oral and Maxillofacial Region: An International Clinicopathologic Study of 13 Cases and Literature Review

Warthin Tumor of the Parotid Gland: The History of an Eponym

A Systematic Review of Adenoid Ameloblastoma: A Newly Recognized Entity

Protease-Activated Receptor 1 (PAR1) Expression Contributes to HPV-Associated Oropharyngeal Cancer Prognosis

p-mTOR, p-ERK and PTEN Expression in Tumor Biopsies and Organoids as Predictive Biomarkers for Patients with HPV Negative Head and Neck Cancer