title: Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma.
abstract: The differential diagnosis between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in MM and less frequently positive in carcinomas, and vice versa. However, in about 10-20% of the cases, the IHC results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy.We stained 45 non-small cell lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include, calretinin, Wilms Tumor 1, cytokeratin 5, podoplanin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM (two-tailed Fisher's Exact Test, P = 5.4 x 10-11). Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 stain helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies.
authors.affiliation: Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
authors.affiliation: Department of Pathology, Queen Medical Center, Honolulu, HI, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shimizu
authors.affiliation: Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Napolitano
authors.affiliation: Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Mika
authors.initials: M
authors.lastname: Tanji
authors.affiliation: Department of Cardiothoracic Surgery, New York University, NYU Langone Medical Center, NY, USA.
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.affiliation: Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Haining
authors.initials: H
authors.lastname: Yang
authors.affiliation: Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pastorino
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008654:Mesothelioma / Q000175:diagnosis* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000276:immunology*; D043222:Ubiquitin Thiolesterase / Q000276:immunology*
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; differential diagnosis; immunohistochemistry; lung cancer; mesothelioma