E-cadherin, N-cadherin, and calretinin in pleural effusions: the good, the bad, the worthless

Diagn Cytopathol. 1999 Mar;20(3):125-30. doi: 10.1002/(sici)1097-0339(199903)20:3<125::aid-dc3>3.0.co;2-v.


The distinction between reactive mesothelial cells (RMC), malignant mesothelioma (MM), and metastatic adenocarcinoma (ACA) in pleural effusions may be impossible based on morphology alone. E-cadherin, N-cadherin, and calretinin are newly described immunocytochemical markers which can potentially be utilized for facilitating this distinction. E-cadherin and N-cadherin are calcium-dependent intercellular adhesion molecules expressed in epithelial cells and mesenchymal/mesothelial cells, respectively. The differential expression of E-cadherins in epithelial cells and N-cadherins in mesothelial cells has been utilized to differentiate reactive mesothelial cells, MMs and ACAs. Calretinin is a calcium-binding protein within the family of EF-hand proteins. It is abundantly expressed in peripheral and central nervous tissues, and has been shown to consistently immunoreact with mesothelial cells. We studied cell block sections from 77 pleural effusions (22 RMC, 26 MM, and 29 ACA) to investigate the potential immunocytochemical use of anti-E-cadherin, anti-N-cadherin, and anti-calretinin antibodies for differentiating between RMC, MM, and ACA in pleural effusions. A modified avidin-biotin peroxidase complex (ABC) method was used. E-cadherin immunostaining was observed in 14% of RMC, 46% of MMs, and 97% of ACAs. A distinct membrane staining pattern was seen in ACAs. The pattern of staining was cytoplasmic in all reactive RMC and varied from membrane to cytoplasmic in MMs. Anti-N-cadherin immunoreacted with 77% of RMC, 35% of MMs, and 48% of ACAs. Twenty-seven percent of RMC, 58% of MMs, and 31% of ACAs immunoreacted with anti-calretinin. Based on these results, we conclude that anti-E-cadherin is a potentially useful marker in the distinction of ACA cells from RMC. However, it is not as useful for the distinction of ACA and MM. Anti-N-cadherin and anti-calretinin did not reliably distinguish between reactive mesothelial, MM, and ACA cells in pleural effusions.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism*
  • Calbindin 2
  • Cytodiagnosis / methods
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Mesothelioma / metabolism
  • Mesothelioma / pathology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Pleural Effusion, Malignant / metabolism*
  • Pleural Effusion, Malignant / pathology
  • S100 Calcium Binding Protein G / metabolism*


  • Biomarkers, Tumor
  • CALB2 protein, human
  • Cadherins
  • Calbindin 2
  • S100 Calcium Binding Protein G