title: Loss of BAP1 Expression Is Very Rare in Pancreatic Ductal Adenocarcinoma.
abstract: BACKGROUND
  Pancreatic cancer is both common and highly lethal and therefore new biomarkers or potential targets for treatment are needed. Loss of BRCA associated protein-1 (BAP1) expression has been found in up to a quarter of intrahepatic cholangiocarcinomas. Given the close anatomical relationship between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma, we therefore sought to investigate the frequency of loss of BAP1 expression in pancreatic ductal adenocarcinoma.
  
  
  METHODS
  The records of the department of Anatomical Pathology Royal North Shore Hospital, Sydney, Australia, were searched for cases of pancreatic ductal adenocarcinoma diagnosed between 1992 and 2014 with material available in archived formalin fixed paraffin embedded tissue blocks. Immunohistochemistry for BAP1 was performed on tissue microarray sections and if staining was equivocal or negative it was confirmed on whole sections. Negative staining for BAP1 was defined as loss of expression in all neoplastic nuclei, with preserved expression in non-neoplastic cells which acted as an internal positive control.
  
  
  RESULTS
  Loss of BAP1 expression was found in only 1 of 306 (0.33%) pancreatic ductal adenocarcinomas. This case was confirmed to demonstrate diffuse loss of expression throughout all neoplastic cells in multiple blocks, consistent with BAP1 loss being an early clonal event. All other cases demonstrated positive expression of BAP1.
  
  
  CONCLUSIONS
  We conclude that, in contrast to intrahepatic cholangiocarcinoma, loss of expression of BAP1 occurs very rarely in pancreatic ductal adenocarcinoma. Therefore BAP1 inactivation is unlikely to be a frequent driver abnormality in pancreatic adenocarcinoma.
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia, 2065.|School of Life Sciences, University of Technology Sydney, Ultimo, NSW, Australia, 2007.
authors.forename: Michael
authors.initials: M
authors.lastname: Tayao
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia, 2065.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia, 2006.|Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia, 2065.
authors.forename: Juliana
authors.initials: J
authors.lastname: Andrici
authors.affiliation: 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: Mahtab
authors.initials: M
authors.lastname: Farzin
authors.affiliation: 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: Adele
authors.initials: A
authors.lastname: Clarkson
authors.affiliation: 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: Loretta
authors.initials: L
authors.lastname: Sioson
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia, 2065.
authors.forename: Nicole
authors.initials: N
authors.lastname: Watson
authors.affiliation: Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia, and Discipline of Surgery, University of Sydney, Sydney, NSW, Australia.|Macquarie University Hospital, Macquarie University, North Ryde, NSW, Australia.
authors.forename: Terence C
authors.initials: TC
authors.lastname: Chua
authors.affiliation: School of Life Sciences, University of Technology Sydney, Ultimo, NSW, Australia, 2007.
authors.forename: Tamara
authors.initials: T
authors.lastname: Sztynda
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia, 2006.|Department of Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia, and Discipline of Surgery, University of Sydney, Sydney, NSW, Australia.|Macquarie University Hospital, Macquarie University, North Ryde, NSW, Australia.
authors.forename: Jaswinder S
authors.initials: JS
authors.lastname: Samra
authors.affiliation: Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia, 2065.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia, 2006.|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, Australia, 2065.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase