9p21 Deletion in the diagnosis of malignant mesothelioma in serous effusions additional to immunocytochemistry, DNA-ICM, and AgNOR analysis

Cancer. 2008 Jun 25;114(3):204-15. doi: 10.1002/cncr.23413.

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 >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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aneuploidy
  • Antigens, Nuclear / analysis*
  • Ascitic Fluid* / pathology
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 9 / genetics*
  • DNA / analysis*
  • Female
  • Humans
  • Image Cytometry*
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence*
  • Male
  • Mesothelioma / diagnosis*
  • Mesothelioma / pathology
  • Middle Aged
  • Peritoneal Neoplasms / diagnosis*
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / pathology
  • Pleural Effusion, Malignant / complications*
  • Pleural Effusion, Malignant / genetics
  • Pleural Effusion, Malignant / pathology
  • Pleural Neoplasms / diagnosis*
  • Pleural Neoplasms / genetics
  • Pleural Neoplasms / pathology

Substances

  • Antigens, Nuclear
  • nucleolar organizer region associated proteins
  • DNA