9p21 Deletion in the diagnosis of malignant mesothelioma in serous effusions additional to immunocytochemistry, DNA-ICM, and AgNOR analysis.
BACKGROUND
The diagnosis of malignant mesothelioma (MM) in serous effusions is difficult but may be achieved by the application of adjuvant methods.


METHODS
The authors cytologically diagnosed 33 effusions as suspicious or positive for MM cells by using DNA-image cytometry (DNA-ICM), immunocytochemistry and AgNOR analysis. The authors further detected 9p21 deletions by chromosomal fluorescence in situ hybridization (FISH). In addition, 31 cases of metastatic carcinomas and 39 of tumor cell-negative effusions were investigated. All diagnoses were confirmed by histologic and/or clinical follow-up.


RESULTS
DNA aneuploidy was found in 71% of MMs, 100% of metastatic carcinomas, and in none of the negative effusions. Calretinin was positive in 100% of MMs, in none of the metastatic carcinomas, and in 94.9% of negative effusions. BerEP4 showed positivity in 15.6% of MMs, 87.1% of metastatic carcinomas, and in none of the negative effusions. With AgNOR analysis, 89.3% of MMs and 96.7% of metastatic carcinomas showed >or=2.5 AgNOR dots as satellites and >or=4.5 as total AgNOR counts. 9p21 deletions were demonstrated in 90.9% of MM cases, 45.2% of metastatic carcinomas, and in none of the negative effusions. By cytology alone, 81.8% of MMs were identified unequivocally. Addition of DNA-ICM improved the prevalence of tumor cell detection to 87.9% and of AgNOR analysis to 97%. The introduction of 9p21 deletions by FISH improved this prevalence to 100%.


CONCLUSIONS
Because of these results, the authors propose the sequential application of immunocytochemistry, DNA-ICM, and AgNOR analysis to establish a cytological diagnosis of malignant mesothelioma in serous effusions. In persistent doubtful diagnoses, the authors recommend fluorescence in situ hybridization to analyze the 9p21 deletion.
Onofre
Fabiana Botelho de Miranda
FB
Institute of Cytopathology, Heinrich-Heine University, Dusseldorf, Germany.
Onofre
Alexandre Sherlley Casimiro
AS
Pomjanski
Natalia
N
Buckstegge
Birgit
B
Grote
Hans Juergen
HJ
Böcking
Alfred
A
D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D034961:Antigens, Nuclear / Q000032:analysis*; D001202:Ascitic Fluid / Q000473:pathology; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004247:DNA / Q000032:analysis*; D005260:Female; D006801:Humans; D019044:Image Cytometry; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000150:complications* / Q000235:genetics / Q000473:pathology; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
D034961:Antigens, Nuclear; C051963:nucleolar organizer region associated proteins; D004247:DNA