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.
OBJECTIVE
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.


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%.


CONCLUSIONS
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.
Fiegl
Michael
M
Department of Internal Medicine, Division of Hematology and Oncology, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. michael.fiegl@uibk.ac.at
Haun
Margot
M
Massoner
Anita
A
Krugmann
Jens
J
Müller-Holzner
Elisabeth
E
Hack
Rene
R
Hilbe
Wolfgang
W
Marth
Christian
C
Duba
Hans-Christoph
HC
Gastl
Günther
G
Grünewald
Kurt
K
D000782:Aneuploidy; D001202:Ascitic Fluid / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D003584:Cytological Techniques; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D060785:Mammaglobin A; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014598:Uteroglobin / Q000235:genetics*
D014408:Biomarkers, Tumor; D060785:Mammaglobin A; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C556448:SCGB2A2 protein, human; D014598:Uteroglobin