Аннотация:Paraneoplastic (onconeural) antigens are the proteins normally specific for the nervous system but it can also be aberrantly expressed in malignant tumors localized outside the immunoprivilege zone. A paraneoplastic antigen recoverin is the first retina-specific protein the aberrant expression of which has been detected in malignant tumors. In this study, we have carried out immunohistochemical investigation of renal tumors for the presence of recoverin expression and analyzed serial specimens of blood sera of patients with these tumors for the presence of autoantibodies against recoverin (AAR). In addition, we have determined the methylation status of the recoverin gene, including the region of the gene promoter up-stream of the first exon and the first exon itself, in renal tumors.
We have carried out immunohistochemical investigation of paraffin sections of 49 renal tumors: cell carcinoma, oncocytoma, papillary adenocarcinoma, and chromophobe adenocarcinoma. The frequencies vary in the range between 50% (renal chromophobe adenocarcinoma) and ~92% (renal oncocytoma).
Also, we have examined 42 serum samples from patients with renal cancer using immunoblotting with recombinant recoverin as an antigen. Autoantibodies against recoverin were detected merely in sera from one patient with papillary adenocarcinoma; while no recoverin-positive sera were found in control patients with urolithiasis.
In addition, methylation analysis by sodium bisulphite sequencing was used to determine the level of DNA methylation in the recoverin gene in renal tumors. It has been demonstrated that demethylation of the certain CpG-dinucleotides in the recoverin gene is involved in the aberrant expression of this protein in renal tumor cells.