High levels of cytokeratin 19 fragments but no evidence of cytokeratins 1, 2, 10/11, 14 or filaggrin in the serum of squamous cell lung carcinoma patients.
The CYFRA 21-1 assay detects circulating fragments of cytokeratin 19, which is a sensitive marker for the diagnosis of lung cancers, particularly squamous cell carcinomas and adenocarcinomas. Epidermis-type proteins, such as cytokeratins 1, 2, 10/11 and 14 or filaggrin, are also expressed in squamous cell carcinomas. These could also be pertinent tumor markers, ideally as sensitive as CYFRA 21-1 and more specific for squamous cell lung cancer. To verify this hypothesis, using monoclonal antibodies produced in our laboratory, we developed immunoassays specific for these proteins. After optimization, the immunoassays were evaluated in sera from 91 controls and 138 patients with squamous cell lung cancer and compared to conventional tumor markers (CEA, SCC Ag and CYFRA 21-1). Less than 14% of the sera were above the lower limit of detection of the cytokeratin- and filaggrin-specific immunoassays. Moreover, part of these positive sera were induced by the presence of interfering heterophilic antibodies in sera. Thus, in patients with squamous cell lung cancer, we confirmed the high diagnostic sensitivity of CYFRA 21-1 (55.6%) but were unable to detect significant levels of epidermis-type cytokeratins or filaggrin.
Miédougé
M
M
Department of Biology and Pathology of the Cell, INSERM CJF 96-02 (IFR30, INSERM-CNRS-UPS-CHU), Toulouse Purpan School of Medicine, University of Toulouse III, Toulouse, France.
Devys
A
A
Simon
M
M
Rouzaud
P
P
Salama
G
G
Reyre
J
J
Pujazon
M
M
Carles
P
P
Serre
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000032:analysis / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D002138:Calibration; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D004817:Epidermis / Q000737:chemistry; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000097:blood* / Q000276:immunology; D053539:Keratin-19; D007633:Keratins / Q000097:blood* / Q000276:immunology; D008171:Lung Diseases / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood* / Q000276:immunology; D010446:Peptide Fragments / Q000097:blood*; D012680:Sensitivity and Specificity; D015843:Serpins
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D053539:Keratin-19; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D015843:Serpins; C102012:antigen CYFRA21.1; C051072:squamous cell carcinoma-related antigen; D007633:Keratins