High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F

To study the clinical features of patients with autoantibodies to centromere protein CENP-F and the frequency of CENP-F autoantibodies in patients with various diseases. Retrospective clinical and serologic study. Thirty-six patients with anti-CENP-F were identified by a characteristic pattern of indirect immunofluorescence (IIF) on HEp-2 cells. Fifty patients with melanoma, 50 with breast cancer, 10 with lung cancer, 354 with systemic sclerosis, 120 with systemic 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), 7538-10,116 (p-F4) and 9242-10,096 (p-F5). The presence of CENP-F antigen was studied in a breast carcinoma cell line, cryosections of breast carcinoma, normal breast tissue and tonsils. 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 sera were available for further study; when tested for reactivity to the recombinant peptides, the sera of 21 of 21 patients with neoplasms and 5 of 12 patients with other diseases bound the C-terminal p-F4 peptide. When the terminal third of the p-F4 peptide (p-F5) was studied, a significant difference in pattern of reactivity was not detected. By comparison, the frequency of reactivity with peptides representing other 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 systemic sclerosis or in unselected sera from various malignancies. CENP-F antigens were identified in breast carcinoma tissue but were rarely observed in normal tissues. A high proportion of individuals with CENP-F antibodies have neoplasia, and there is a bias among their sera for reactivity with determinants in the carboxy terminal domain of CENP-F. CENP-F antigens appear to be highly expressed in malignant tissues.