title: Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma.
abstract: Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma. We searched the computerized database of the Department of Anatomical Pathology, Royal North Shore Hospital, Australia, for all cases of gynecologic and peritoneal serous carcinomas and mesotheliomas diagnosed between 1998 and 2014. Immunohistochemistry for BAP1 was then performed on tissue microarray sections. Cases with completely absent nuclear staining in the presence of a positive internal control in nonneoplastic cells were considered negative. If staining was equivocal (eg, absent nuclear staining but no internal control), staining was repeated on whole sections. Loss of BAP1 expression was found in only 1 of 395 (0.3%) serous carcinomas but in 6 of 9 (67%) abdominal mesotheliomas (P < .001) and 131 of 277 (47%) thoracic mesotheliomas (P < .001). We conclude that BAP1 loss occurs extremely infrequently in gynecologic and peritoneal serous adenocarcinomas, whereas it is very common in mesotheliomas including abdominal mesothelioma. Therefore, although positive staining for BAP1 cannot be used to exclude a diagnosis of mesothelioma, loss of BAP1 expression can be used to very strongly support a pathological diagnosis of abdominal mesothelioma over serous carcinoma.
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065.
authors.forename: Juliana
authors.initials: J
authors.lastname: Andrici
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006.
authors.forename: Jason
authors.initials: J
authors.lastname: Jung
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065.
authors.forename: Amy
authors.initials: A
authors.lastname: Sheen
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW Australia 2065.
authors.forename: Lisa
authors.initials: L
authors.lastname: D'Urso
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065.
authors.forename: Loretta
authors.initials: L
authors.lastname: Sioson
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065.
authors.forename: Justine
authors.initials: J
authors.lastname: Pickett
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Parkhill
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006.
authors.forename: Brandon
authors.initials: B
authors.lastname: Verdonk
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Wardell
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006.
authors.forename: Arjun
authors.initials: A
authors.lastname: Singh
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW Australia 2065.
authors.forename: Adele
authors.initials: A
authors.lastname: Clarkson
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006.
authors.forename: Nicole
authors.initials: N
authors.lastname: Watson
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065; Histopath Pathology, North Ryde, NSW, Australia 2113.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Toon
authors.affiliation: Sydney Medical School, University of Sydney, NSW Australia 2006; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW Australia 2065; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW Australia 2065; Sydney Vital Translational Research Centre, Royal North Shore Hospital, Pacific Highway St Leonards, NSW 2065. Electronic address: affgill@med.usyd.edu.au.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
mesh_terms: D000008:Abdominal Neoplasms / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008654:Mesothelioma / Q000175:diagnosis*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D010534:Peritoneal Neoplasms / Q000175:diagnosis*; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*; D043222:Ubiquitin Thiolesterase / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; BRCA1-associated protein 1; Serous adenocarcinoma