A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis

Kinoshita, Yoshiaki; Hamasaki, Makoto; Yoshimura, Masayo; Matsumoto, Shinji; Sato, Ayuko; Tsujimura, Tohru; Ueda, Hitoshi; Makihata, Satoshi; Kato, Fumiki; Iwasaki, Atsushi; Nabeshima, Kazuki

doi:10.1016/j.lungcan.2018.09.019

Cited by 46 publications

(30 citation statements)

References 52 publications

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“…Immunostaining was performed with either the anti-MTAP mouse monoclonal antibody (clone 2G4; Abnova, Taipei, Taiwan; 1:100 dilution; room temperature (RT) 30 min) or antihuman BAP1 mouse monoclonal antibody (clone C4, 1:50 dilution; RT 45 min; Santa Cruz Biotechnology, Santa Cruz, CA, USA) using previously described methods. 27,28,32,35,45,46 BAP1 IHC/ICC was performed on both cell blocks and smear preparations. Meanwhile, MTAP IHC was limited only to cell blocks because MTAP ICC does not perform well in smear preparations in our experience (unpublished data).…”

Section: Ihc Assaymentioning

confidence: 99%

“…BAP1 IHC/ICC revealed staining in the nucleus, and BAP1 loss was defined as a complete loss of nuclear staining. 27,28,32 Cytoplasmic reactivity to BAP1 was interpreted as a nonspecific reaction. MTAP IHC revealed cytoplasmic as well as nuclear staining, and MTAP loss as detected by IHC was defined as cytoplasmic staining at an intensity lower than the internal positive control.…”

Section: Ihc Assaymentioning

confidence: 99%

“…MTAP IHC revealed cytoplasmic as well as nuclear staining, and MTAP loss as detected by IHC was defined as cytoplasmic staining at an intensity lower than the internal positive control. 27,28,32,45,46 We evaluated the reactivity in at least 100 mesothelial cells per sample. We have previously observed a bimodal distribution in the proportion of mesothelioma cells positive for BAP1 or MTAP IHC; 27,28 stain-positive cases exhibit a high proportion of positivity (>70%), and stain-negative cases exhibit a low proportion of positivity (<30%).…”

Section: Ihc Assaymentioning

confidence: 99%

“…FISH studies were conducted on smear preparations or cell blocks using Vysis LSI p16/CEP 9 probe (Abbott Japan, Tokyo, Japan) as previously described. 14,26,28,32,46 Lymphocytes and histiocytes in each preparation served as internal controls and showed two signals per FISH probe. The use of internal controls helped to exclude preanalytical factors like fixation or sample processing as reasons for the loss of FISH signals.…”

Section: Fish Assaymentioning

confidence: 99%

“…11,18 Accumulating evidence has shown the efficacy of genomic-based assays probing for genetic alterations in MPM, in the differentiation of MPM from RMH/RMC. These assays include fluorescence in situ hybridization (FISH) detection of homozygous deletion of the 9p21 locus (9p21 FISH), 14,[22][23][24][25][26][27][28][29][30] immunohistochemical (IHC) detection of loss of methylthioadenosine phosphorylase (MTAP) expression (MTAP IHC) as a surrogate assay for 9p21 FISH 27,28,[30][31][32][33] and IHC detection of BRCA1-associated protein 1 (BAP1) expression loss (BAP1 IHC). 25,[28][29][30][34][35][36][37] Positive findings in these assays (expression loss or homozygous deletion) have never been associated with the reactive process of mesothelial proliferations.…”

Section: Introductionmentioning

confidence: 99%

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Genomic‐based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma

Kinoshita

Hamasaki

Matsumoto

et al. 2020

Pathology International

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BRCA1‐associated protein 1 (BAP1) or methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) or 9p21 fluorescence in situ hybridization (FISH) are useful for the diagnosis of malignant pleural mesothelioma (MPM). However, the effect of these assays on the diagnostic yield of effusion cytology in MPM cases with suspicious cytomorphology or the diagnostic challenges in BAP1 or MTAP IHC have not been fully elucidated. Two cohorts of cytologic preparations obtained from pleural effusions were examined: MPM cases in cohort 1 were used to evaluate whether BAP1 or MTAP IHC or 9p21 FISH increase the diagnostic yield of effusion cytology; cohort 2 included cases suspicious for MPM, to which BAP1 or MTAP IHC was applied to clarify the challenges in the clinical assessment of these assays. In cohort 1 (n = 28), either assay elevated 62.5% of class II or III cases to class V. In cohort 2 (n = 139), 21.7% of BAP1 immunocytochemistry in smears and 10.6% of BAP1 IHC and 9.4% of MTAP IHC in cell blocks, were identified to be challenging. The application of genomic‐based assays increased the diagnostic yield of effusion cytology in the diagnosis of MPM. However, diagnostic challenges limit the application of these assays in some cases.

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Section: Ihc Assaymentioning

confidence: 99%

Section: Ihc Assaymentioning

confidence: 99%

Section: Ihc Assaymentioning

confidence: 99%

Section: Fish Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomic‐based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma

Kinoshita

Hamasaki

Matsumoto

et al. 2020

Pathology International

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Diagnostic mesothelioma biomarkers in effusion cytology

Eccher¹,

Girolami

Lucenteforte

et al. 2021

Cancer Cytopathology

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Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin‐like growth factor 2 mRNA‐binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1‐associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin‐dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.

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Investigation of MTAP and BAP1 staining loss and P16/CDKN2A deletion in pleural cytology specimens and its role in the diagnosis of mesothelioma

Şeker,

Tekin,

et al. 2024

Diagnostic Cytopathology

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BackgroundMesothelioma is a malignant neoplasm with a poor survival rate. We aimed to investigate the importance of BAP1, MTAP (IHC), and p16/CDKN2A homozygous deletion (FISH) in cytologic material obtained from pleural effusion sampling, which is a less invasive procedure in the diagnosis of mesothelioma.MethodsOur study discussed pleural cytology samples of cases with histopathologically proven mesothelioma diagnoses between 2017 and 2022. As the control group, materials that had pleural effusion sampling for other reasons and reactive mesothelial hyperplasia were included in the study. Cell blocks prepared from these materials were subjected to fluorescent in situ hybridization for p16/CDKN2A homozygous deletion and immunohistochemistry for BAP1 and MTAP.ResultsThe specificity of the P16/CDKN2A homozygous deletion in diagnosing mesothelioma is 100%. Its sensitivity is 68.75%. The specificity of BAP1 immunohistochemical nuclear expression loss is 95%, while the sensitivity is 60%. Loss of nuclear expression of MTAP alone has the lowest specificity and sensitivity, with a specificity of 86% and a sensitivity of 43%. The highest sensitivity is reached when BAP1 loss and p16/CDKN2A homozygous deletion are evaluated together, increasing to 81%. The specificity is 95%.ConclusionIt has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.

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A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis

Cited by 46 publications

References 52 publications

Genomic‐based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma

Genomic‐based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma

Diagnostic mesothelioma biomarkers in effusion cytology

Investigation of MTAP and BAP1 staining loss and P16/CDKN2A deletion in pleural cytology specimens and its role in the diagnosis of mesothelioma

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