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Challenges and limitation of MTAP immunohistochemistry in diagnosing desmoplastic mesothelioma/sarcomatoid pleural mesothelioma with desmoplastic features
Institution:1. Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan;2. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kean, Thailand;3. Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, Chikushino, Japan;4. Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan;5. Department of Pathology, National Hospital Organization Kinki-chuo Chest Medical Center, Osaka, Japan;6. Department of Pathology, Tokyo Women''s Medical University Yachiyo Medical Center, Yachiyo, Japan;7. Department of Pathology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan;8. Department of Pathology, Osaka Habikino Medical Center, Osaka, Japan;9. Department of Thoracic Surgery, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan;1. Division of Pathology, Thammasat University Hospital, Pathum Thani, Thailand;2. Division of Pathology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand;3. Advanced Digital Simulation Center, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand;1. Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing 100730, China;2. Department of Pathology, Beijing Chuiyangliu Hospital, Beijing 100022, China;1. Department of Pathology and Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China;2. Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China;3. Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100069, China;4. Department of Pathology and Key Laboratory for Xinjiang Endemic & Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832002, China;5. Department of Pathology, Shanghai PuDong GongLi Hospital, Shanghai, 200135, China;1. Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677, Japan;2. Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan;3. Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan;4. Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan;5. Department of Surgery, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan;6. Department of Molecular Pathology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677, Japan;7. University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Abstract:AimGenomic-based ancillary assays including immunohistochemistry (IHC) for BRCA-1 associated protein-1 (BAP1) and methylthioadenosine phosphorylase (MTAP), and fluorescence in situ hybridization (FISH) for CDKN2A are effective for differentiating pleural mesothelioma (PM) from reactive mesothelial proliferations. We previously reported a combination of MTAP and BAP1 IHC effectively distinguishes sarcomatoid PM from fibrous pleuritis (FP). Nevertheless, cases of sarcomatoid PM with desmoplastic features (desmoPM) are encountered where the IHC assessment is unclear.Methods and resultsWe evaluated assessment of MTAP IHC, BAP1 IHC, and CDKN2A FISH in 20 desmoPM compared to 24 FP. MTAP and BAP1 IHC could not be assessed in 11 (55 %) and 10 (50 %) cases, respectively, due to loss or faint immunoreactivity of internal positive control cells, while CDKN2A FISH could be evaluated in all cases. The sensitivities for MTAP loss, BAP1 loss, and CDKN2A homozygous deletion in desmoPM were 40 %, 10 %, and 100 %. A combination of MTAP loss and BAP1 loss yielded 45 % of sensitivity.ConclusionsMTAP IHC is a useful surrogate diagnostic marker in differentiating ordinary sarcomatoid PM from FP, but its effectiveness is limited in desmoPM. CDKN2A FISH is the most effective diagnostic assays with 100 % sensitivity and specificity in discriminating desmoPM from FP in the facilities where the FISH assay is available.
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