Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma

Wu, Di; Hiroshima, Kenzo; Yusa, Toshikazu; Ozaki, Daisuke; Koh, Eitetsu; Sekine, Yasuo; Matsumoto, Shinji; Nabeshima, Kazuki; Sato, Ayuko; Tsujimura, Tohru; Yamakawa, Hisami; Tada, Yuji; Shimada, Hideaki; Tagawa, Masatoshi

doi:10.1016/j.anndiagpath.2016.10.010

Cited by 44 publications

(35 citation statements)

References 17 publications

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“…Moreover, in 33% of our cases with low-grade spindle cells components, we showed that HD (p16) was definitively more sensitive in favor of malignancy present in 62.5% (5 of 8) of the low-grade spindle cell component of biphasic type; whereas on these cases, BAP1 loss by IHC alone on the epithelioid (4 of 8) or retained (1 of 8) component was observed. These results are in agreement with previous reports published by Hwang et al 29 and Wu et al 31 on challenges in differentiating sarcomatoid or desmoplastic mesothelioma from a cellular organizing pleuritis. They observed that BAP1 loss was seen in 3 of 20 (15%) and deletion of p16 by FISH was seen in 16 of 20 (80%) of such difficult lesion cases.…”

Section: Discussionsupporting

confidence: 94%

“…p16 loss of expression was not considered as a definitive argument of malignancy in the absence of homozygous CDKN2A (p16) deletion by FISH analysis. [28][29][30][31] CDKN2A (p16) FISH. CDKN2A (p16) FISH for detection of homozygous deletion of CDKN2A (p16) was performed using the dual-color FISH analysis for the CDKN2A locus (9p21) and the centromere of the chromosome 9 (CEP-9), using the ZytoVision (Bremerhaven, Germany) probe (ZytoLight SPEC CDKN2A/CEN 9 Dual Color Probe, # Z-2063-200) and was used from fresh serial recuts of 3 m to 5 m in thickness from the FFPE block stored in the correct conditions.…”

Section: Ihc and Molecular Analysismentioning

confidence: 99%

“…The presence of homozygous CDKN2A(p16) deletion by FISH analysis on the spindle cells component was also regarded as a criterion for malignancy. [29][30][31] On the other hand, heterozygous deletion (HD) was not considered a criterion for malignancy. To avoid technical bias, a two-step assessment with one trained technician and one molecular biologist or pathologist was involved in the case review.…”

Section: Ihc and Molecular Analysismentioning

confidence: 99%

“…BAP1 and CDKN2A(p16) HDs are considered markers of malignancy. [28][29][30][31] When BAP1 loss was observed on the spindle cell component alone it was considered as a decisive argument for malignancy and when retained it was considered indeterminate of malignancy. 25,28,29 NS).…”

Section: Molecular Assessment As a Tool For Histopathologic Groupingmentioning

confidence: 99%

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New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center

Galateau-Salle

Stang

Nicholson

et al. 2018

Journal of Thoracic Oncology

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The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.

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Section: Discussionsupporting

confidence: 94%

Section: Ihc and Molecular Analysismentioning

confidence: 99%

Section: Ihc and Molecular Analysismentioning

confidence: 99%

Section: Molecular Assessment As a Tool For Histopathologic Groupingmentioning

confidence: 99%

See 2 more Smart Citations

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center

Galateau-Salle

Stang

Nicholson

et al. 2018

Journal of Thoracic Oncology

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“…However, BAP1 loss is relatively uncommon in the sarcomatoid subtype. Therefore, BAP1 immunohistochemistry has a relatively high specificity, but low sensitivity [ 87 , 88 , 89 ]. In contrast to BAP1 loss, the CDKN2A deletion is observed more frequently in the sarcomatoid subtype than in the epithelioid/biphasic subtype [ 88 , 89 , 90 ].…”

Section: Lung Carcinoma Vs Malignant Mesotheliomamentioning

confidence: 99%

Update on Immunohistochemistry for the Diagnosis of Lung Cancer

Inamura

2018

Cancers

120

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Immunohistochemistry is a widely available technique that is less challenging and can provide clinically meaningful results quickly and cost-efficiently in comparison with other techniques. In addition, immunohistochemistry allows for the evaluation of cellular localization of proteins in the context of tumor structure. In an era of precision medicine, pathologists are required to classify lung cancer into specific subtypes and assess biomarkers relevant to molecular-targeted therapies. This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma. Major pitfalls in evaluating immunohistochemical results are also described.

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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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Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma

Cited by 44 publications

References 17 publications

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center

Update on Immunohistochemistry for the Diagnosis of Lung Cancer

Diagnostic mesothelioma biomarkers in effusion cytology

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