PMID- 32678499 OWN - NLM STAT- MEDLINE DCOM- 20210222 LR - 20210222 IS - 1934-6638 (Electronic) IS - 1934-662X (Linking) VI - 128 IP - 12 DP - 2020 Dec TI - Testing for BAP1 loss and CDKN2A/p16 homozygous deletion improves the accurate diagnosis of mesothelial proliferations in effusion cytology. PG - 939-947 LID - 10.1002/cncy.22326 [doi] AB - BACKGROUND: A number of ancillary tests have been developed that aid in the diagnosis of mesothelioma in cytology specimens. The aim of this retrospective study was to determine whether testing for BAP1 and CDKN2A/p16 status in effusion specimens preceding the tissue diagnosis of mesothelioma would improve diagnostic accuracy and allow an earlier diagnosis of malignancy. METHODS: The study cohort included 99 matched cytology fluid specimens from 74 patients with a surgical specimen diagnosis of malignant mesothelioma (67 epithelioid, 7 biphasic, 55 pleural, and 19 peritoneal). BAP1 immunohistochemistry and p16 fluorescence in situ hybridization (FISH) were performed retrospectively. RESULTS: BAP1 or p16 FISH testing revealed a loss in 7 of 18 (39%) samples originally categorized as benign/reactive, 20 of 33 (61%) interpretable samples categorized as atypical, and 10 of 14 (71%) cases suspicious for mesothelioma. In some cases, the diagnosis of mesothelioma could have been made up to 9 months before biopsy. Similarly, loss of BAP1 or p16 was found in 28 of 30 (93%) samples categorized as malignant, with some cases diagnosable up to 6 months before biopsy. Overall, loss of BAP1 and/or CDKN2A/p16 homozygous deletion would change the diagnostic interpretation in 37 of 60 (62%) (P = .07) effusion specimens, particularly in pleural effusions (32 of 48 samples) (P = .002). The sensitivity of morphologic interpretation alone was 30.3%; however, adding testing for BAP1 and p16 resulted in an increase in sensitivity to 68.7%. (P < .0001). CONCLUSION: These findings suggest that routine use of BAP1 immunochemistry and p16 FISH as adjunctive tests improves the diagnostic accuracy of cytology specimens and potentially allows an earlier diagnosis of malignant mesothelioma. CI - (c) 2020 American Cancer Society. FAU - Chevrier, Martin AU - Chevrier M AD - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Monaco, Sara E AU - Monaco SE AUID- ORCID: 0000-0003-3039-4445 AD - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Jerome, Jacob A AU - Jerome JA AD - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Galateau-Salle, Francoise AU - Galateau-Salle F AD - Centre National Referent MESOPATH, Centre Leon Berard, Lyon, France. FAU - Churg, Andrew AU - Churg A AD - Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada. FAU - Dacic, Sanja AU - Dacic S AUID- ORCID: 0000-0003-4197-3354 AD - Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. LA - eng PT - Journal Article DEP - 20200717 PL - United States TA - Cancer Cytopathol JT - Cancer cytopathology JID - 101499453 RN - 0 (BAP1 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Tumor Suppressor Proteins) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Cyclin-Dependent Kinase Inhibitor p16/*genetics MH - Cytodiagnosis/*methods MH - Female MH - Follow-Up Studies MH - Genetic Testing/methods MH - Homozygote MH - Humans MH - Male MH - Mesothelioma, Malignant/*diagnosis/genetics/surgery MH - Middle Aged MH - Peritoneal Neoplasms/diagnosis/genetics/surgery MH - Pleural Effusion/genetics/*pathology MH - Pleural Neoplasms/diagnosis/genetics/surgery MH - Prognosis MH - Retrospective Studies MH - *Sequence Deletion MH - Tumor Suppressor Proteins/*genetics MH - Ubiquitin Thiolesterase/*genetics MH - Young Adult OTO - NOTNLM OT - BAP1 OT - cytopathology OT - effusion cytology OT - mesothelioma OT - p16 EDAT- 2020/07/18 06:00 MHDA- 2021/02/23 06:00 CRDT- 2020/07/18 06:00 PHST- 2020/04/22 00:00 [received] PHST- 2020/06/17 00:00 [revised] PHST- 2020/06/17 00:00 [accepted] PHST- 2020/07/18 06:00 [pubmed] PHST- 2021/02/23 06:00 [medline] PHST- 2020/07/18 06:00 [entrez] AID - 10.1002/cncy.22326 [doi] PST - ppublish SO - Cancer Cytopathol. 2020 Dec;128(12):939-947. doi: 10.1002/cncy.22326. Epub 2020 Jul 17.