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Original Research: CANCER |

Fluorescence In Situ Hybridization in the Definitive Diagnosis of Malignant Mesothelioma in Effusion Cytology

Spasenija Savic, MD; Noreli Franco, PhD; Bruno Grilli; Audrey de Vito Barascud; Michelle Herzog; Beata Bode, MD; Heinz Loosli, MD; Peter Spieler, MD; René Schönegg, MD; Inti Zlobec, PhD; Douglas P. Clark, MD; James G. Herman, MD; Lukas Bubendorf, MD
Author and Funding Information

From the Institute for Pathology (Drs Savic, Zlobec, and Bubendorf; Mr Grilli; and Mss de Vito Barascud and Herzog), University Hospital Basel, Basel, Switzerland; the Department of Pathology (Dr Bode), Institute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland; the Institute for Pathology (Dr Loosli), University Bern, Bern, Switzerland; the Institute for Pathology (Drs Spieler and Schönegg), Cantonal Hospital St. Gallen, St. Gallen, Switzerland; and the Division of Tumor Biology (Drs Franco and Herman), The Sidney Kimmel Comprehensive Cancer Center, and the Department of Pathology (Dr Clark), The Johns Hopkins Medical Institutions, Baltimore, MD.

Correspondence to: Spasenija Savic, MD, Institute for Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland; e-mail: ssavic@uhbs.ch


Funding/Support: This work was funded by a grant from the Krebsliga beider Basel [Grant 14-2008].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(1):137-144. doi:10.1378/chest.09-1951
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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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