Friday, February 29th, 2008.

Cancer Cytopathology. 2008 Feb 27 [Epub ahead of print] [Link]

Onofre FB, Onofre AS, Pomjanski N, Buckstegge B, Grote HJ, Böcking A.

Institute of Cytopathology. Heinrich‐Heine University, Dusseldorf, Germany.

Abstract

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.

Keywords: 9p21, CDKN2A, fluorescence in situ hybridization, DNA-ICM, AgNOR analysis, immunocytochemistry, mesothelioma, effusion

Glossary

prevalence

a measure of the proportion of persons in the population with a certain disease at a given time.

in situ

in place; localized and confined to one area. A very early stage of cancer.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

detection

finding disease. Early detection means that the disease is found at an early stage, before it has grown large or spread to other sites. Note many forms of cancer can reach an advanced stage without causing symptoms. Mammography can help to find breast cancer early, and the PSA blood test is useful in finding prostate cancer.

DNA

(dee-ok-see-ri-bo-new-CLAY-ic) abbreviation for deoxyribonucleic acid. DNA holds genetic information on cell growth, division, and function.

cytology

(cy-tahl-uh-gee) the branch of science that deals with the structure and function of cells.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

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