Novel marker D2-40, combined with calretinin, CEA, and TTF-1: an optimal set of immunodiagnostic markers for pleural mesothelioma

Cancer. 2007 Mar 1;109(5):933-8. doi: 10.1002/cncr.22477.


Background: Malignant pleural mesothelioma is a challenging disease with regard to diagnosis and treatment; early and accurate diagnosis would lead to appropriate therapeutic strategies, including extrapleural pneumonectomy. Immunohistochemistry has proven valuable for the diagnosis of the most common epithelioid mesothelioma, although it is often difficult to differentiate it from pulmonary or metastatic adenocarcinoma with absolute certainty if a single antibody is employed. The current study was designed to identify an immunodiagnostic panel for pleural mesothelioma.

Methods: Large surgical specimens from 66 cases with pleural mesothelioma and 66 with lung adenocarcinoma were immunohistochemically reevaluated under uniform conditions. The antibodies examined were directed against the novel mesothelial marker D2-40, as well as calretinin, CEA, and TTF-1.

Results: For mesothelioma the sensitivities of D2-40 and calretinin were 84.8% and 87.9%, respectively, and their specificities were both 95.5%. For adenocarcinoma, the sensitivities of CEA and TTF-1 were 95.5% and 92.4%, respectively, and their specificities were both 100%. Immunoreactivity to D2-40 and calretinin was observed in most areas of epithelioid differentiation in mesothelioma. Western blots also showed higher levels of D2-40 antigen in pleura invaded by epithelioid mesothelioma as compared with unaffected pleura.

Conclusions: These data strongly suggest the significant usefulness of D2-40 and calretinin as positive markers, and of CEA and TTF-1 as negative markers, for pleural mesothelioma. The 4-antibody immunohistochemical panel showed high sensitivity and specificity with regard to differentiation of epithelioid mesothelioma from lung adenocarcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism
  • Adult
  • Aged
  • Antibodies, Monoclonal / metabolism*
  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Calbindin 2
  • Carcinoembryonic Antigen / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism
  • Male
  • Mesothelioma / diagnosis*
  • Mesothelioma / metabolism
  • Middle Aged
  • Nuclear Proteins / metabolism
  • Pleural Neoplasms / diagnosis*
  • Pleural Neoplasms / metabolism
  • S100 Calcium Binding Protein G / metabolism
  • Sensitivity and Specificity
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • CALB2 protein, human
  • Calbindin 2
  • Carcinoembryonic Antigen
  • NKX2-1 protein, human
  • Nuclear Proteins
  • S100 Calcium Binding Protein G
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • monoclonal antibody D2-40