PMID- 33197684 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20220531 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 150 DP - 2020 Dec TI - Homozygous deletion of CDKN2A in malignant mesothelioma: Diagnostic utility, patient characteristics and survival in a UK mesothelioma centre. PG - 195-200 LID - S0169-5002(20)30673-5 [pii] LID - 10.1016/j.lungcan.2020.10.020 [doi] AB - BACKGROUND: Detection of homozygous deletion of the p16 gene (CDKN2A) by fluorescence in situ hybridization (FISH) has been investigated as an ancillary technique in the diagnosis of malignant mesothelioma. METHOD: This retrospective study reviewed the results of all p16 FISH tests performed at a regional mesothelioma centre from February 2012 to November 2019 in cases of possible mesothelioma to examine the diagnostic utility of this test as well as patients characteristics and survival in p16 FISH positive mesothelioma versus p16 FISH negative mesothelioma. RESULTS: P16 FISH testing was requested in 216 pathological samples in the study period. The test failure rate was 4% (10/216). Median time from request to result was 10 days (IQR 7-13, range 1-30). The sensitivity, specificity, NPV and PPV were 60 %, 100 %, 39 % and 100 % respectively. There were no false positive results and this genetic aberration was only detected in cases of mesothelioma. The prevalence of p16 FISH positive mesothelioma was higher in cytological specimens compared to histological specimens (75 % vs 58 %, p = 0.03) and lower in women compared to men (33 % vs 66 %, p = 0.003). P16 FISH positive mesothelioma was associated with significantly worse survival (median overall survival 285 vs 339 days, p = 0.0018). This remained significant after adjusting for confounding variables (OR 4.4, 95 %CI 1.84-11.14, p = 0.001). CONCLUSIONS: In this study, 60 % of mesotheliomas harbour a homozygous deletion of CDKN2A and can be accurately, reliably and efficiently identified by p16 FISH testing. This test can be embedded within routine practice in mesothelioma pathways to enhance diagnostic accuracy. CI - Copyright (c) 2020. Published by Elsevier B.V. FAU - Marshall, Kelly AU - Marshall K AD - Pleural Medicine, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Jackson, Susan AU - Jackson S AD - Pleural Medicine, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Jones, Jennifer AU - Jones J AD - Pleural Medicine, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Holme, Jayne AU - Holme J AD - Pleural Medicine, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Lyons, Judith AU - Lyons J AD - Pleural Medicine, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Barrett, Emma AU - Barrett E AD - Department of Medical Statistics, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Taylor, Paul AU - Taylor P AD - Department of Medical Oncology, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Bishop, Paul AU - Bishop P AD - Department of Cellular Pathology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Hodgson, Clare AU - Hodgson C AD - Department of Cytogenetics, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK. FAU - Green, Michael AU - Green M AD - Department of Cytogenetics, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK. FAU - Telford, Nicholas AU - Telford N AD - Department of Cytogenetics, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK. FAU - Evison, Matthew AU - Evison M AD - Pleural Medicine, North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. Electronic address: m.evison@nhs.net. LA - eng PT - Journal Article DEP - 20201105 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) SB - IM MH - *Cyclin-Dependent Kinase Inhibitor p16/genetics MH - Female MH - Genes, p16 MH - Homozygote MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Lung Neoplasms/diagnosis/genetics MH - Male MH - *Mesothelioma/diagnosis/genetics MH - *Mesothelioma, Malignant MH - Retrospective Studies MH - Sequence Deletion MH - United Kingdom OTO - NOTNLM OT - CDKN2A OT - Mesothelioma OT - p16 FISH EDAT- 2020/11/17 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/11/16 20:10 PHST- 2020/09/16 00:00 [received] PHST- 2020/10/22 00:00 [revised] PHST- 2020/10/27 00:00 [accepted] PHST- 2020/11/17 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/11/16 20:10 [entrez] AID - S0169-5002(20)30673-5 [pii] AID - 10.1016/j.lungcan.2020.10.020 [doi] PST - ppublish SO - Lung Cancer. 2020 Dec;150:195-200. doi: 10.1016/j.lungcan.2020.10.020. Epub 2020 Nov 5.