Aberrantly expressed cytokeratin 1, a tumor-associated autoantigen in papillary thyroid carcinoma.
Papillary thyroid carcinoma (PTC) is a somewhat puzzling disease, combining a propensity to metastasize with an indolent clinical course. The often pronounced T cell-dominated inflammatory infiltrate seen in PTC tumors has prompted us to search for signs of a tumor-induced immune response. In previous studies, we have demonstrated large tumor-specific deposits of IgG and complement in PTC tissue and isolated a putative target antigen. This investigation examines the presence of autoantibodies to cytokeratin 1, a high m.w. cytokeratin normally expressed only in suprabasal keratinocytes, in the serum and tumor tissue of PTC patients. Using immunoprecipitation and Western blot, cytokeratin 1-reactive autoantibodies were demonstrated in 80% of the PTC sera tested, and tumor-derived antibodies were shown to precipitate cytokeratin 1. Using immunohistochemistry, cytokeratins 1 and 10 were found in a large proportion of PTC tumors (39/44) but were absent from normal thyrocytes of most PTC-bearing glands. Our results indicate that this protein is expressed aberrantly in neoplastic cells and is immunogenic in this context.
Lucas
S D
SD
Department of Surgery, Uppsala University Hospital, Sweden. Steven.Lucas@kirurgi.uu.se
Ek
B
B
Rask
L
L
Rastad
J
J
Akerström
G
G
Juhlin
C
C
D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007633:Keratins / Q000276:immunology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
D001323:Autoantibodies; D001324:Autoantigens; D014408:Biomarkers, Tumor; D007633:Keratins