Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry. (February 2017)

• Record Type: Journal Article
• Authors: Hida, Tomoyuki; Hamasaki, Makoto; Matsumoto, Shinji; Sato, Ayuko; Tsujimura, Tohru; Kawahara, Kunimitsu; Iwasaki, Akinori; Okamoto, Tatsuro; Oda, Yoshinao; Honda, Hiroshi; Nabeshima, Kazuki
• Is Part Of: Lung cancer. Volume 104(2017)
• Page Start: 98
• Page End: 105
• Publication Date: 2017-02
• Subjects: BAP1 BRCA1 associated protein 1 -- CEA carcinoembryonic antigen -- DAPI 4′, 6-diamidino-2-phenylindole -- EPP extrapleural pneumonectomy -- FISH fluorescence in situ hybridization -- HD homozygous deletion -- IHC immunohistochemistry -- L/D loss or decrease -- MPM malignant pleural mesothelioma -- MTAP methylthioadenosine phosphorylase -- PD pleurectomy and decortication -- RMH reactive mesothelial hyperplasia -- ROC receiver-operating characteristic -- RT room temperature -- SSC saline-sodium citrate -- TTF-1 thyroid transcription factor-1 -- VATS video-assisted thoracic surgery -- WHO World Health Organization -- WT-1 Wilms' tumor-1; Malignant pleural mesothelioma -- MTAP -- BAP1 -- Immunohistochemistry -- 9p21 FISH -- Diagnosis; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.12.017
• Languages: English
• ISSNs: 0169-5002

Abstract

Abstract: Objectives: Differentiating malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH) is still challenging. Detection of homozygous deletion (HD) of 9p21 region including p16 INK4A ( p16 ) by fluorescence in situ hybridization (FISH) and immunohistochemical detection of loss of BRCA1 associated protein 1 (BAP1), are reliable markers for MPM diagnosis. However, not all laboratories are equipped to perform 9p21 FISH; immunohistochemistry (IHC) is a more common and feasible technique. Thus, we sought to develop a IHC-based method that could predict the deletion of p16 in MPM in concordance with 9p21 FISH. Materials and methods: We examined the expression of the 9p21.3-related proteins (p14, p15, p16, and methylthioadenosine phosphorylase (MTAP)) and BAP1 using IHC in 51 MPM and 25 RMH cases, and assessed their correlation with HD of p16 detected by FISH. The diagnostic usefulness of IHC of the 9p21.3-related proteins and BAP1 and their combinations was assessed using the cut-off values set by receiver operating characteristic (ROC) analysis. Results: Among the 9p21.3-related proteins, MTAP IHC findings showed best concordance with 9p21 FISH results (kappa coefficient of 0.69) and a specificity of 100%. We also examined the combinations of MTAP IHC with the other products. The loss of p16 and MTAP had better concordance (kappa coefficient of 0.71), although lower specificity (85%). For differentiating MPM from RMH, only MTAP showed 100% specificity among the 9p21.3-related proteins, as did BAP1 IHC and 9p21 FISH. Among BAP1 combinations, only that of BAP1 with MTAP showed 100% specificity. Its sensitivity was 76.5%, which was lower than BAP1 IHC and 9p21 FISH combination (84.3%), but higher than BAP1 IHC alone (60.8%) or 9p21 FISH alone (60.8%). Conclusions: A combination of MTAP or BAP1 loss detected by IHC can likely detect MPM with good sensitivity and 100% specificity, and serve as useful ancillary IHC for discriminating MPM from RMH.