Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma

Int J Surg Pathol. 2013 Oct;21(5):493-501. doi: 10.1177/1066896913491320. Epub 2013 Jun 17.


We compared claudin-4 with Ber-EP4 and carcinoembryonic antigen as markers to distinguish mesothelioma from lung adenocarcinoma, poorly differentiated lung squamous cell carcinoma, and serous adenocarcinoma of the uterus or ovary. All mesothelioma specimens were negative for claudin-4, but 3 of 18 specimens were focally positive for Ber-EP4. In contrast, lung adenocarcinoma including poorly differentiated adenocarcinoma was highly positive for claudin-4, but expression of Ber-EP4 and carcinoembryonic antigen varied widely. Claudin-4 in poorly differentiated squamous cell carcinoma had a lower positive expression rate than in adenocarcinoma. Granular claudin-4 immunoreactivity was conspicuous in poorly differentiated squamous cell carcinoma; this immunoreactive pattern was also observed in mesothelioma. Claudin-4 was thus considered very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells. However, it should be mentioned that claudin-4 has a limit in discrimination between squamous cell carcinoma from mesothelioma.

Keywords: Ber-EP4; carcinoembryonic antigen; carcinoma; claudin-4; malignant mesothelioma.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Claudin-4 / analysis
  • Claudin-4 / biosynthesis*
  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / metabolism
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Mesothelioma / diagnosis*
  • Mesothelioma / metabolism
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / metabolism
  • Uterine Neoplasms / diagnosis
  • Uterine Neoplasms / metabolism


  • Biomarkers, Tumor
  • Claudin-4