We report on the identification of
autoantigens commonly recognized by sera from patients with
breast cancer. We selected ten sera from patients with invasive
ductal carcinoma (IDC) of the breast with high titer
IgG autoantibodies for biopanning of a T7 phage
breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential
breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with
breast cancer [15 patients with
ductal carcinoma in situ (
DCIS) and 75 patients with IDC of the breast], with 51 non-
cancer control sera and with sera from 21 patients with systemic
autoimmune diseases. A 12-phage
breast cancer predictor group was constructed with phage inserts recognized by sera from patients with
breast cancer and not by non-
cancer or autoimmune control sera (P < 0.0001). Several
autoantigens including
annexin XI-A, the p80 subunit of the
Ku antigen,
ribosomal protein S6, and other unknown
autoantigens could significantly discriminate between
breast cancer and non-
cancer control sera. Biopanning with three different sera led to the cloning of partial
cDNA sequences identical to
annexin XI-A.
IgG autoantibodies reacting with the
amino acid 41-74 sequence of
annexin XI-A were found in 19% of all women with
breast cancer but in 60% of sera from women with
DCIS of the breast. In addition, partial sequences identical to
annexin XI-A,
nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product,
ribosomal protein S6,
cyclin K, elongation factor-2, Grb2-associated
protein 2, and other unknown
proteins could distinguish
DCIS from IDC of the breast and appear to be potential
biomarkers for the diagnosis of
breast cancer.