A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Cancer Cytopathol. 2018 Jan;126(1):54-63. doi: 10.1002/cncy.21928. Epub 2017 Oct 20.


Background: Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions.

Methods: The authors examined IHC expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45 cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC expression of MTAP was compared with the deletion status of 9p21 FISH.

Results: MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks.

Conclusions: A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54-63. © 2017 American Cancer Society.

Keywords: 9p21 fluorescence in situ hybridization; cell block; malignant pleural mesothelioma; pleural effusion; reactive mesothelial hyperplasia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma / diagnosis*
  • Mesothelioma / pathology
  • Middle Aged
  • Pleural Effusion / pathology*
  • Pleural Neoplasms / diagnosis*
  • Pleural Neoplasms / pathology
  • Purine-Nucleoside Phosphorylase / analysis*
  • Tumor Suppressor Proteins / analysis*
  • Ubiquitin Thiolesterase / analysis*


  • BAP1 protein, human
  • Tumor Suppressor Proteins
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase
  • Ubiquitin Thiolesterase

Supplementary concepts

  • Mesothelioma, Malignant