title: 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.
abstract: 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.
authors.affiliation: Department of Pathology I, University of Brescia, Spedali Civili Brescia, Piazzale Spedali Civili 1, Brescia, 25124, Italy. facchett@med.unibs.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gentili
authors.forename: Luisa
authors.initials: L
authors.lastname: Bercich
authors.forename: Marcella
authors.initials: M
authors.lastname: Falchetti
authors.forename: Regina
authors.initials: R
authors.lastname: Tardanico
authors.forename: Carla
authors.initials: C
authors.lastname: Baronchelli
authors.forename: Laura
authors.initials: L
authors.lastname: Lucini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santin
authors.forename: Bruno
authors.initials: B
authors.lastname: Murer
mesh_terms: D001202:Ascitic Fluid / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D062506:Claudin-4; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis*; D008654:Mesothelioma / Q000737:chemistry* / Q000473:pathology; D010537:Peritoneum / Q000473:pathology*; D010994:Pleura / Q000473:pathology*; D010996:Pleural Effusion / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C568157:CLDN4 protein, human; D062506:Claudin-4; D008565:Membrane Proteins