Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology

Cancer Cytopathol. 2014 Apr;122(4):299-306. doi: 10.1002/cncy.21392. Epub 2014 Jan 13.

Abstract

Background: Adenocarcinoma can be challenging to distinguish from malignant mesothelioma in effusions, and this distinction often requires ancillary studies and clinical correlation. Immunohistochemistry for claudin-4, a tight-junction-associated protein, has recently been shown to distinguish adenocarcinoma from malignant mesothelioma, mostly in surgical specimens. Our aim was to validate and assess the immunoreactivity profile of claudin-4 in a large series of malignant effusions.

Methods: We evaluated 159 malignant effusions (84 adenocarcinomas and 75 malignant mesotheliomas). Claudin-4 immunohistochemistry was performed on cell-block paraffin sections and scored for staining intensity, staining pattern (cytoplasmic versus membranous), and percentage of positive tumor cells. Appropriate positive and negative controls were used throughout.

Results: All cases of mesothelioma were negative for claudin-4 (0 of 64). Eighty-three of 84 cases of adenocarcinoma were positive (99%); 1 case of serous carcinoma was negative. Most adenocarcinomas showed strong and diffuse membranous staining (71 of 84; 84%); 12 cases (14%) showed membranous staining of moderate intensity. The overall sensitivity for adenocarcinoma was 99% (83 of 84).

Conclusions: Claudin-4 immunohistochemistry effectively distinguishes adenocarcinoma from malignant mesothelioma with high sensitivity and specificity in the evaluation of malignant effusions.

Keywords: adenocarcinoma; claudin-4; cytology; effusion; mesothelioma.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / pathology*
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Claudin-4 / analysis*
  • Cytodiagnosis / methods
  • Databases, Factual
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Mesothelioma / chemistry
  • Mesothelioma / pathology*
  • Middle Aged
  • Pleural Effusion, Malignant / chemistry
  • Pleural Effusion, Malignant / pathology*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Claudin-4