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Combination of Cytology, Fluorescence In Situ Hybridization for Aneuploidy, and Reverse-Transcriptase Polymerase Chain Reaction for Human Mammaglobin/Mammaglobin B Expression Improves Diagnosis of Malignant Effusions

From the Departments of Internal Medicine, Pathology, and Obstetrics and Gynecology, Divisions of Hematology and Oncology and General Internal Medicine, and Institute of Medical Biology and Human Genetics, University of Innsbruck, Innsbruck; Department of Pulmonology, Natters Hospital, Natters, Austria

Address reprint requests to Michael Fiegl, MD, Division of Hematology and Oncology, Innsbruck University Hospital, Anichstraße 35, A-6020 Innsbruck, Austria; e-mail: michael.fiegl{at}uibk.ac.at

PURPOSE: The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity. The aim of this study was to improve tumor cell detection in effusions by molecular approaches.

MATERIALS AND METHODS: A total of 157 effusions from patients with tumors and 72 effusions from patients without a history or evidence of malignancy were included in this study. All effusion specimens were evaluated in parallel by cytology, fluorescence in situ hybridization (FISH) for aneuploidy, and reverse-transcriptase polymerase chain reaction (RT-PCR) for expression of human mammaglobin (hMAM) and mammaglobin B (hMAM-B).

RESULTS: In effusions from patients with tumors, the sensitivities of tumor cell detection by cytology, FISH, and hMAM and hMAM-B detection were 46.2%, 53.3%, 36.4%, and 57.7%, respectively. The corresponding specificities were 94.4%, 97.0%, 87.1%, and 88.6%. Notably, a high percentage of effusions containing malignant cells were in fact transudates, indicating the necessity for molecular diagnostic work-up of transudates collected from patients with tumors. Dependent on the tumor type, the use of appropriate marker combinations improved tumor cell detection in effusions significantly. By combining all four diagnostic tests, a positive test result indicating the presence of malignancy was achieved in 81.1%, with a fairly good specificity of 70.1%.

CONCLUSION: Molecular techniques are definitely useful to detect malignancy in cytologically negative effusions. Tumor cell detection in effusions can be significantly improved by FISH and PCR techniques applying appropriate molecular markers. This finding should help to improve tumor staging, prognostic assessment, and treatment monitoring.

Supported in part by the "Tiroler Verein zur Förderung der Krebsforschung," by the "Verein zur Förderung von Forschung und Fortbildung in molekularer Genetik und Diagnostik internistischer Erkrankungen," and by the "Hans und Blanca Moser-Stiftung."

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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