TY - JOUR
T1 - Fluorescence In Situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology
AU - Savic, Spasenija
AU - Franco, Noreli
AU - Grilli, Bruno
AU - De Vito Barascud, Audrey
AU - Herzog, Michelle
AU - Bode, Beata
AU - Loosli, Heinz
AU - Spieler, Peter
AU - Schönegg, René
AU - Zlobec, Inti
AU - Clark, Douglas P.
AU - Herman, James G.
AU - Bubendorf, Lukas
N1 - Funding Information:
Author contributions: Dr Savic: contributed to coordinating the study, carrying out the MSP analysis, collecting the data, performing the data analysis, drafting the manuscript, and reading and approving the final version of the manuscript. Dr Franco: contributed to MSP analysis and reading and approving the final version of the manuscript. Mr Grilli: contributed to carrying out the FISH analysis, FISH scoring, and reading and approving the final version of the manuscript. Ms de Vito Barascud: contributed to carrying out the FISH analysis, FISH scoring, and reading and approving the final version of the manuscript. Ms Herzog: contributed to carrying out the FISH analysis, FISH scoring, and reading and approving the final version of the manuscript. Dr Bode: contributed to sample and clinical follow-up collection and reading and approving the final version of the manuscript. Dr Loosli: contributed to sample and clinical follow-up collection and reading and approving the final version of the manuscript. Dr Spieler: contributed to sample and clinical follow-up collection and reading and approving the final version of the manuscript. Dr Schönegg: contributed to sample and clinical follow-up collection and reading and approving the final version of the manuscript. Dr Zlobec: contributed to performing statistical data analyses and helping in manuscript writing and reading and approving the final version of the manuscript. Dr Clark: contributed to sample and clinical follow-up collection and reading and approving the final version of the manuscript. Dr Herman: contributed to the design of the MSP, interpretation of MSP results, and reading and approving the final version of the manuscript. Dr Bubendorf: contributed to conceiving of the study, designing the study, helping to draft the manuscript, and reading and approving the final version of the manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Bubendorf received speaker's honorary and financial research support from Abbott Molecular, Inc. Dr Herman is a consultant to Oncomethylome Sciences. Drs Savic, Franco, Bode, Loosli, Spieler, Schönegg, Zlobec, and Carter; Mr Grilli, and Mss de Vito Barascud, and Herzog have reported no potential conflict of interests with any company/organization whose products or services may have been discussed in this article.
PY - 2010/7/1
Y1 - 2010/7/1
N2 - 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.
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.
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U2 - 10.1378/chest.09-1951
DO - 10.1378/chest.09-1951
M3 - Article
C2 - 20139227
AN - SCOPUS:77954481138
SN - 0012-3692
VL - 138
SP - 137
EP - 144
JO - Diseases of the chest
JF - Diseases of the chest
IS - 1
ER -