PMID- 20139227 OWN - NLM STAT- MEDLINE DCOM- 20100817 LR - 20181204 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 138 IP - 1 DP - 2010 Jul TI - Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology. PG - 137-44 LID - 10.1378/chest.09-1951 [doi] AB - BACKGROUND: Distinction of malignant mesothelioma (MM) from reactive mesothelial cells (RM) in effusions is notoriously difficult. The aim of our study was to test chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in the diagnosis of MM in effusion cytology and to explore the potential role of p16, p14, and p15 gene methylation as an alternative mechanism of tumor suppressor gene inactivation. METHODS: Fifty-two effusions of biopsy-proven MM and 28 benign effusions were retrospectively analyzed by multitarget FISH assay for aberrations of chromosomes 3, 7, 17, and 9p21. In case of a negative result, the corresponding MM biopsy specimen was analyzed. Methylation-specific polymerase chain reaction (MSP) for p16, p14, and p15 was performed on FISH-negative MM biopsy specimens. RESULTS: Seventy-nine percent of effusions with biopsy-proven MM had chromosomal aberrations, with loss of 9p21 as the most common finding. All benign effusions were FISH negative. Sensitivity, specificity, and positive and negative predictive values for detection of MM by FISH were 79%, 100%, 100%, and 72%, respectively. Six of nine FISH-negative effusions with biopsy-proven MM were also FISH negative in the MM biopsy specimens. Four of five FISH-negative biopsy specimens showed promoter methylation in p16 and p14 as compared with one of 12 benign controls. CONCLUSIONS: FISH is a sensitive and highly specific method for the definitive diagnosis of MM in effusion cytology. In the subset of FISH-negative MM, tumor suppressor genes on the chromosomal region 9p21 are often inactivated by promoter methylation. FAU - Savic, Spasenija AU - Savic S AD - Institute for Pathology, University Hospital Basel, Schonbeinstrasse 40, 4031 Basel, Switzerland. ssavic@uhbs.ch FAU - Franco, Noreli AU - Franco N FAU - Grilli, Bruno AU - Grilli B FAU - Barascud, Audrey de Vito AU - Barascud Ade V FAU - Herzog, Michelle AU - Herzog M FAU - Bode, Beata AU - Bode B FAU - Loosli, Heinz AU - Loosli H FAU - Spieler, Peter AU - Spieler P FAU - Schonegg, Rene AU - Schonegg R FAU - Zlobec, Inti AU - Zlobec I FAU - Clark, Douglas P AU - Clark DP FAU - Herman, James G AU - Herman JG FAU - Bubendorf, Lukas AU - Bubendorf L LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100205 PL - United States TA - Chest JT - Chest JID - 0231335 RN - 0 (DNA, Neoplasm) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biopsy MH - DNA, Neoplasm/analysis MH - Diagnosis, Differential MH - Female MH - Genes, p16 MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Male MH - Mesothelioma/genetics/*pathology MH - Middle Aged MH - Pleural Effusion/diagnosis MH - Pleural Effusion, Malignant/genetics/*pathology MH - Polymerase Chain Reaction MH - Retrospective Studies EDAT- 2010/02/09 06:00 MHDA- 2010/08/18 06:00 CRDT- 2010/02/09 06:00 PHST- 2010/02/09 06:00 [entrez] PHST- 2010/02/09 06:00 [pubmed] PHST- 2010/08/18 06:00 [medline] AID - S0012-3692(10)60358-3 [pii] AID - 10.1378/chest.09-1951 [doi] PST - ppublish SO - Chest. 2010 Jul;138(1):137-44. doi: 10.1378/chest.09-1951. Epub 2010 Feb 5.