ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2024
Comparison of Immunohistochemistry, Next-generation Sequencing and Fluorescence In Situ Hybridization for Detection of MTAP Loss in Pleural Mesothelioma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Immunohistochemical Loss of MTAP as a Diagnostic and Prognostic Surrogate ofDiagnostics (Basel, Switzerland) · 2026Review
- Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario.Cancer research · 2026Review
- Review
- MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.Cells · 2025Review
- Loss of MTAP expression is not an accurate surrogate for CDKN2A homozygous deletions in peritoneal mesothelioma.Histopathology · 2025Article
- Current approaches, barriers, and future directions in pleural mesothelioma diagnostics: results from an Italian National Survey.Pathologica · 2025Article
- Assessment of CDKN2A homozygous and heterozygous deletions in gliomas across multiple detection platforms.BMC cancer · 2025Article
- Correlation of Histologic Features with Gene Alterations in Pleural Mesothelioma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Advances in diagnosis and management of pleural mesothelioma: the Danish clinical guidelines.European clinical respiratory journal · 2025Review
- Mesothelioma: molecular pathology and biomarkers.Pathologie (Heidelberg, Germany) · 2024Review
- Editorial: Asbestos and disease genomics: is mesothelioma a genomic paradigm?Frontiers in toxicology · 2024Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
9p21 deletions involving MTAP/CDKN2A genes are detected in diffuse pleural mesotheliomas (DPM) but are absent in benign mesothelial proliferations. Loss of MTAP expression by immunohistochemistry (IHC) is well accepted as a surrogate for 9p21 deletion to support a diagnosis of DPM. Accurate interpretation can be critical in the diagnosis of DPM, but variations in antibody performance may impact interpretation. The objectives of this study were to compare the performance of MTAP monoclonal antibodies (mAbs) EPR6893 and 1813 and to compare MTAP expression by IHC with 9p21 copy number status in DPM. Cytoplasmic expression of MTAP IHC with mAbs EPR6893 (ab126770; Abcam) and 1813 (NBP2-75730, Novus Biologicals) was evaluated in 56 DPM (47 epithelioid, 7 biphasic, and 2 sarcomatoid) profiled by targeted next-generation sequencing. 9p21 Copy number status was assessed by Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) analysis and also by CDKN2A fluorescence in situ hybridization in discrepant cases when material was available. MTAP mAb 1813 showed stronger immunoreactivity, more specific staining, and no equivocal interpretations compared to mAb EPR6893 which showed equivocal staining in 19 (34%) of cases due to weak or heterogenous immunoreactivity, lack of definitive internal positive control, and/or nonspecific background staining. MTAP expression with mAb 1813 showed near perfect agreement with 9p21 copy number by combined FACETS/fluorescence in situ hybridization calls (κ = 0.85; 95% CI, 0.71-0.99; P < .001). MTAP IHC with mAb 1813 was 96% sensitive, 86% specific, and 93% accurate for 9p21 homozygous deletion. The findings of this study suggest that interpretation of MTAP IHC is improved with mAb 1813 because mAb EPR6893 was often limited by equivocal interpretations. We show that MTAP IHC and molecular assays are complementary in detecting 9p21 homozygous deletion. MTAP IHC may be particularly useful for low tumor purity samples and in low-resource settings.
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