Kenzo Hiroshima1,2,3, Di Wu2, Shinji Hamakawa4, Shingo Tsuruoka5, Daisuke Ozaki6, Hideki Orikasa7, Mizue Hasegawa8, Eitetsu Koh9, Yasuo Sekine9, Yoko Yonemori6, Kazuki Nabeshima10, Shoutaro Tsuji11, Yohei Miyagi12, Kohzoh Imai13. 1. Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Chiba, Japan. 2. Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan. 3. Department of Medicine, Sodegaura Satsukidai Hospital, Sodegaura, Japan. 4. Department of Clinical Laboratory, Showa General Hospital, Kodaira, Japan. 5. Department of Pathology, Saitama Medical Center, JCHO, Saitama, Japan. 6. Department of Pathology, Chiba Rosai Hospital, Ichihara, Japan. 7. Department of Pathology, Kawasaki Municipal Hospital, Kawasaki, Japan. 8. Department of Respiratory Medicine, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan. 9. Department of Thoracic Surgery, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan. 10. Department of Pathology, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan. 11. Division of Cancer Therapeutics, Kanagawa Cancer Center Research Institute, Yokohama, Japan. 12. Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. 13. Research Platform Office, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Abstract
BACKGROUND: The specificity and sensitivity of HEG1 for malignant mesothelioma (MM) is high. The use of BAP1/MTAP immunohistochemistry (IHC) is recommended to separate benign and malignant mesothelial proliferations. We determined how ancillary techniques can be used for the cytological diagnosis of MM with effusion. METHODS: Cell blocks from effusions from cases with MM, reactive mesothelial cells (RMCs), and carcinomas were analyzed by IHC with HEG1, BAP1, and MTAP and with homozygous deletion (HD) of CDKN2A by fluorescence in situ hybridization. Staining scores were calculated for IHC by adding the number of categories for the staining intensity and the staining extension. RESULTS: HEG1 was positive in all (41/41) MMs, but negative in carcinomas, except for ovarian carcinomas. Overall 76.9% (20/26) of RMCs and 28.6% (6/21) of ovarian carcinomas expressed HEG1. BAP1 loss was found in 71.1% of MMs, but none was found in RMCs. MTAP loss was found in 76.2% of MMs, but none was found in RMCs. 73.9% of MMs harbored HD of CDKN2A. There was concordance between loss of MTAP and HD of CDKN2A in 95% of MMs. CONCLUSION: HEG1 is a good marker for mesothelial differentiation in effusion cytology. HD of CDKN2A is frequently observed in cell blocks from effusions of MMs, and MTAP IHC may act as a surrogate for HD of CDKN2A. Cell block analysis is recommended for effusions of unknown origins with the following methods: IHC with HEG1 and claudin 4 to validate the mesothelial origin, followed by BAP1 and MTAP IHC to confirm malignancy.
BACKGROUND: The specificity and sensitivity of HEG1 for malignant mesothelioma (MM) is high. The use of BAP1/MTAP immunohistochemistry (IHC) is recommended to separate benign and malignant mesothelial proliferations. We determined how ancillary techniques can be used for the cytological diagnosis of MM with effusion. METHODS: Cell blocks from effusions from cases with MM, reactive mesothelial cells (RMCs), and carcinomas were analyzed by IHC with HEG1, BAP1, and MTAP and with homozygous deletion (HD) of CDKN2A by fluorescence in situ hybridization. Staining scores were calculated for IHC by adding the number of categories for the staining intensity and the staining extension. RESULTS:HEG1 was positive in all (41/41) MMs, but negative in carcinomas, except for ovarian carcinomas. Overall 76.9% (20/26) of RMCs and 28.6% (6/21) of ovarian carcinomas expressed HEG1. BAP1 loss was found in 71.1% of MMs, but none was found in RMCs. MTAP loss was found in 76.2% of MMs, but none was found in RMCs. 73.9% of MMs harbored HD of CDKN2A. There was concordance between loss of MTAP and HD of CDKN2A in 95% of MMs. CONCLUSION:HEG1 is a good marker for mesothelial differentiation in effusion cytology. HD of CDKN2A is frequently observed in cell blocks from effusions of MMs, and MTAP IHC may act as a surrogate for HD of CDKN2A. Cell block analysis is recommended for effusions of unknown origins with the following methods: IHC with HEG1 and claudin 4 to validate the mesothelial origin, followed by BAP1 and MTAP IHC to confirm malignancy.