title: BRCA1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: A Large Retrospective Study.
abstract: Malignant pleural mesothelioma (MPM) is a highly aggressive disease with limited therapeutic options. Histological subtype remains among the most reliable prognostic factors, because the epithelioid subtype associated with the best prognosis and the sarcomatoid subtype with the worst. The biphasic subtype has an intermediate prognosis, but its definitive histological diagnosis may be challenging owing to the difficulty of assessing the neoplastic nature of the stromal component. Recent data identified BRCA1-associated protein 1 gene (BAP1) as one of the most frequently mutated genes in MPM. Immunohistochemical testing for BRCA1-associated protein 1 (BAP1) has been proposed to be predictive for the detection of BAP1 mutation in neoplastic cells. The aim of the present study was to define the diagnostic usefulness of immunohistochemical determination of BAP1 in MPM, with clinicopathological correlation.
  
  
  
  A series of 143 MPMs were investigated for BAP1 protein expression in correlation with clinical and pathological data, including with a newly proposed nuclear grade. A pilot series of 20 selected cases were also investigated for BAP1 mutational status.
  
  
  
  Negative nuclear staining for BAP1 occurred in 62% of MPMs (including 27% with a cytoplasmic pattern) and was significantly associated with the presence of BAP1 mutation, epithelioid subtype, and a better prognosis. In a subgroup of cases, the pattern of expression of BAP1 in stromal cells supported their distinction as reactive versus neoplastic, thus helping achieve the correct classification of biphasic histological subtype.
  
  
  
  We showed that BAP1 protein determination is a diagnostic tool to correctly distinguish biphasic MPM from epithelial subtypes with an atypical/activated reactive stroma and an independent prognostic parameter in MPM.
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy. Electronic address: luisella.righi@unito.it.
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Duregon
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Vatrano
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Izzo
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Giorcelli
authors.affiliation: Department of Medical Science, University of Turin, Turin, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Rondón-Lagos
authors.affiliation: Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ascoli
authors.affiliation: Department of Surgical Sciences, City of Health and Science Hospital, University of Turin, Turin, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.affiliation: Department of Statistical Sciences, University of Padua, Padua, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ventura
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy; Pathology Unit, City of Health and Science Hospital, University of Turin, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D009154:Mutation; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor
keywords: BAP1 mutation; Histology; Malignant mesothelioma; Pleura; Prognosis