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9p21 Deletion in the diagnosis of malignant mesothelioma in serous effusions additional to immunocytochemistry, DNA‐ICM, and AgNOR analysis
Author(s) -
Onofre Fabiana Botelho de Miranda,
Onofre Alexandre Sherlley Casimiro,
Pomjanski Natalia,
Buckstegge Birgit,
Grote Hans Juergen,
Böcking Alfred
Publication year - 2008
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23413
Subject(s) - pathology , immunocytochemistry , serous fluid , mesothelioma , medicine , serous membrane , cytology , fluorescence in situ hybridization , biology , chromosome , gene , biochemistry
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 ≥2.5 AgNOR dots as satellites and ≥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. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.