title: Glyco- and immunohistochemical refinement of the differential diagnosis between mesothelioma and metastatic carcinoma and survival analysis of patients.
abstract: The aim of this study was to analyse the diagnostic value of selected glyco- and immunohistochemical probes for discrimination between mesotheliomas and metastatic carcinomas within the pleura, and to evaluate prognostic indicators in the tested panel. A panel of nine markers (five antibodies, two neoglycoproteins, and labelled hyaluronic acid) was applied to a total of 264 specimens with mesotheliomas (118 cases) and metastatic carcinomas in the pleura (146 cases); the material consisted exclusively of surgical specimens. The diagnosis obtained by standard procedures was further substantiated through a detailed follow-up and clear-cut descriptions of primary sites. The metastatic tumours originated from the lung (82 cases), breast (47 cases), colon (three cases), and kidney (two cases); in 12 cases, however, the tumour origin could not be ascertained. In detail, the probes tested included antibodies against carcinoembryonic antigen (CEA), vimentin, calretinin, mesothelial cells (HBME-1), calcyclin and keratin-5; and also biotinylated neoglycoproteins with ganglioside GM1 and N-acetyl-D-glucosamine (GlcNAc) as the ligand part, and hyaluronic acid. Carrier-immobilized ganglioside GM1 and hyaluronic acid displayed the highest specificity and sensitivity for mesotheliomas, followed by calretinin and HBME-1, whereas keratin-5 and vimentin were of low specificity (43% and 52%, respectively). Metastatic carcinomas could be discerned by CEA detection and application of GlcNAc-bearing neoglycoprotein with similar sensitivity (76% and 72%, respectively) and specificity (91% and 86%, respectively). In cases of breast carcinoma, the maximum specificity (59%) and sensitivity (67%) were low for all markers. Patients with mesothelioma survived longer than those with metastatic carcinoma, especially those with detectable binding sites for hyaluronic acid. No association of tumour type and binding properties of the other applied probes with survival of the patients could be found at a statistically significant level. It is concluded that in routine practice, the application of carrier-immobilized GM1, hyaluronic acid, and antibodies against calretinin and HBME-1 is useful for confirmation of mesothelioma, whereas the detection of CEA and GlcNAc-specific binding sites is useful for distinguishing metastatic carcinoma from mesothelioma. Despite the rather infrequent occurrence of mesotheliomas in women, particular attention should be given to exclude or confirm metastatic breast carcinoma in cases of unknown history or long metastatic interval.
authors.affiliation: Department of Pathology, Thoraxklinik, Heidelberg, Germany. klkayser@lung.de
authors.forename: K
authors.initials: K
authors.lastname: Kayser
authors.forename: G
authors.initials: G
authors.lastname: Böhm
authors.forename: S
authors.initials: S
authors.lastname: Blum
authors.forename: M
authors.initials: M
authors.lastname: Beyer
authors.forename: S
authors.initials: S
authors.lastname: Zink
authors.forename: S
authors.initials: S
authors.lastname: André
authors.forename: H J
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D000117:Acetylglucosamine / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D003937:Diagnosis, Differential; D005069:Evaluation Studies as Topic; D005260:Female; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D006820:Hyaluronic Acid / Q000276:immunology; D007633:Keratins / Q000276:immunology; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D012680:Sensitivity and Specificity; D014746:Vimentin / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D005732:Gangliosides; D014746:Vimentin; D007633:Keratins; D006820:Hyaluronic Acid; D000117:Acetylglucosamine