PMID- 37916370 OWN - NLM STAT- MEDLINE DCOM- 20231107 LR - 20231107 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 27 IP - 20 DP - 2023 Oct TI - Contribution of BAP1 loss and p16 (CDKN2A) deletion analysis to the definitive diagnosis of mesothelioma in effusion cytology. PG - 10001-10007 LID - 34180 [pii] LID - 10.26355/eurrev_202310_34180 [doi] AB - OBJECTIVE: The cytological diagnosis of mesothelioma is a controversial issue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of BRCA1-associated protein (1) (BAP1) loss and p16 (CDKN2A) homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids. MATERIALS AND METHODS: Between 2019-2022, 21 pleural and peritoneal fluid samples diagnosed with atypical mesothelial proliferation in our institution were included in the study. The slides of the cases that underwent BAP1 immunohistochemistry (IHC) were retrieved from the archive and re-examined. Homozygous deletion (HD) of p16 (CDKN2A) was investigated by the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples. At least 100 atypical mesothelial cells were counted in each case, and the HD threshold value was >10%. RESULTS: The mean age of the cases was 63.47 years (34-90 years), female/male ratio was 3/1. Of the pleural mesothelioma cases, 16 were epithelioid, 2 were biphasic, and 1 were sarcomatoid. Two cases were diagnosed with peritoneal well-differentiated papillary mesothelioma (WDPM). BAP1 loss was observed in 11 (69%) of 16 cases. HD deletion of p16 (CDKN2A) was seen in 11 (58%) patients with FISH. The HD threshold value was 10-20% in 6 of the cases, 30-50% in 3 cases, and above 90% in 2 cases. While HD deletion was observed in p16 (CDKN2A) in all biphasic and sarcomatoid cases (n=3), no deletion was observed in peritoneal WDPM (n=2). Positivity was observed with at least one method in 12 (86%) of 14 pleural mesotheliomas who underwent both BAP1 IHC and p16 (CDKN2A) FISH. Due to technical reasons, the FISH signal could not be obtained in two cell blocks, so no results could be obtained. CONCLUSIONS: Asbestos exposure in areas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cytological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Although the FISH method applied to cell blocks has cytology-specific limitations and difficulties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis. FAU - Aydogdu, G AU - Aydogdu G AD - Department of Pathology, Faculty of Medicine, Dicle University Diyarbakir, Turkey. gulay.aydogdu@balikesir.edu.tr. FAU - Ozekinci, S AU - Ozekinci S LA - eng PT - Journal Article PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (BAP1 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Cyclin-Dependent Kinase Inhibitor Proteins) RN - 0 (Tumor Suppressor Proteins) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers, Tumor/analysis MH - Cyclin-Dependent Kinase Inhibitor p16/genetics MH - Cyclin-Dependent Kinase Inhibitor Proteins MH - Homozygote MH - In Situ Hybridization, Fluorescence MH - *Lung Neoplasms/genetics MH - *Mesothelioma/diagnosis/genetics/metabolism MH - *Mesothelioma, Malignant MH - *Pleural Neoplasms MH - Sequence Deletion MH - Tumor Suppressor Proteins/genetics/analysis MH - Ubiquitin Thiolesterase/genetics MH - Adult MH - Aged MH - Aged, 80 and over EDAT- 2023/11/02 06:42 MHDA- 2023/11/03 06:43 CRDT- 2023/11/02 04:43 PHST- 2023/11/03 06:43 [medline] PHST- 2023/11/02 06:42 [pubmed] PHST- 2023/11/02 04:43 [entrez] AID - 34180 [pii] AID - 10.26355/eurrev_202310_34180 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2023 Oct;27(20):10001-10007. doi: 10.26355/eurrev_202310_34180.