Virchows Archiv

, Volume 451, Issue 3, pp 669–680 | Cite as

Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions

  • Fabio Facchetti
  • Silvia Lonardi
  • Francesca Gentili
  • Luisa Bercich
  • Marcella Falchetti
  • Regina Tardanico
  • Carla Baronchelli
  • Laura Lucini
  • Alessandro Santin
  • Bruno Murer
Original Article


We evaluated the usefulness of the tight-junction associated protein Claudin 4 (CL-4) in the diagnosis of mesothelioma and mimickers, analyzing biopsies from 454 tumors, including 82 mesotheliomas, 336 carcinomas of different origin (278 primary, 58 metastatic to serosae), 36 nonepithelial spindle cell neoplasms, as well as 97 cytological samples from reactive effusions (12), mesothelioma (23) and metastatic carcinomas (62). CL-4 was consistently negative in normal and reactive mesothelium, as well as in all 82 mesotheliomas. In contrast, strong reactivity was found in 57/58 serosal metastasis, and in 245/278 primary carcinomas, with uppermost expression (150/153) in those most frequently involved in the differential with mesothelioma (lung, breast, gastrointestinal tract, pancreas, ovary, primary serous papillary carcinoma of peritoneum). On effusions, reactive and neoplastic mesothelial cells were regularly negative, while metastatic tumor cells stained positively in 60/62 (96.8%) cases. Among spindle cell neoplasms, only 2/9 biphasic synovial sarcomas and 4/4 follicular dendritic cell sarcomas stained positively. Results indicate that CL-4 reacts with the majority of epithelial neoplasms that often metastasize to serous membranes, representing a pancarcinoma marker with extremely high sensitivity and specificity. CL-4 may be considered a primary immunohistochemical reagent to rule out the diagnosis of mesothelioma.


Claudin 4 Tight junctions Mesothelioma Carcinoma Follicular dendritic cells Immunohistochemistry 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Fabio Facchetti
    • 1
  • Silvia Lonardi
    • 1
  • Francesca Gentili
    • 1
  • Luisa Bercich
    • 1
  • Marcella Falchetti
    • 1
  • Regina Tardanico
    • 1
  • Carla Baronchelli
    • 1
  • Laura Lucini
    • 1
  • Alessandro Santin
    • 2
  • Bruno Murer
    • 3
  1. 1.Department of Pathology IUniversity of BresciaBresciaItaly
  2. 2.Department of Obstetrics and GynaecologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Department of PathologyMestre HospitalMestreItaly

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