HIGH-FREQUENCY OF NEOPLASIA IN PATIENTS WITH AUTOANTIBODIES TO CENTROMERE PROTEIN CENP-F

Objective: To study the clinical features of patients with autoantibod ies to centromere protein CENP-F and the frequency of CENP-F autoantib odies in patients with various diseases. Design: Retrospective clinica l and serologic study. Methods: Thirty-six patients with anti-CENP-F w ere identified by a characteristic pattern of indirect immunofluoresce nce (IIF) on HEp-2 cells. Fifty patients with melanoma, 50 with breast cancer, 10 with lung cancer, 354 with systemic sclerosis, 120 with sy stemic lupus erythematosus and 50 with rheumatoid arthritis were also studied. Recombinant proteins were produced from 5 CENP-F cDNA clones representing amino acids 2192-3317 (p-F1), 5561-7126 (p-F2), 5892-6883 (p-F3), 7538-10116 (p-F4) and 9242-10096 (p-F5). The presence of CENP -F antigen was studied in a breast carcinoma cell Line, cryosections o f breast carcinoma, normal breast tissue and tonsils. Results: Twenty- two of 36 patients with CENP-F antibodies had neoplasms. breast (9/22) and lung (5/22) cancer were the most common diagnoses. Thirty-three s era were available for further study; when tested for reactivity to th e recombinant peptides, the sera of 21 of 21 patients with neoplasms a nd 5 of 12 patients with other diseases bound the C-terminal p-F4 pept ide. When the terminal third of the p-F4 peptide fp-FS) was studied, a significant difference in pattern of reactivity was not detected. By comparison, the frequency of reactivity with peptides representing oth er domains of CENP-F was less than that with p-F4 (p-F2 > p-F3 > p-F1) . CENP-F autoantibodies were not found in any of the control sera from patients with systemic lupus erythematosus, rheumatoid arthritis or s ystemic sclerosis or in unselected sera from various malignancies. CEN P-F antigens were identified in breast carcinoma tissue but were rarel y observed in normal tissues. Conclusions: A high proportion of indivi duals with CENP-F antibodies have neoplasia, and there is a bias among their sera for reactivity with determinants in the carboxy terminal d omain of CENP-F. CENP-F antigens appear to be highly expressed in mali gnant tissues.