title: Autoimmunity to the M(r) 32,000 subunit of replication protein A in breast cancer.
abstract: OBJECTIVE
  We sought to identify autoantigens recognized by antibodies in breast cancer patient sera with potential diagnostic or prognostic significance.
  
  
  METHODS
  Serum from a female breast cancer patient exhibiting a high titer antinuclear antibody was used to screen a HeLa cDNA expression library, leading to the cloning of a cDNA for the M(r) 32,000 subunit of replication protein A (RPA32). RPA32 expression and localization were assayed in autologous tumor by monoclonal antibody staining. A specific ELISA using recombinant protein was used to screen sera from 801 breast cancer patients and 65 controls.
  
  
  RESULTS
  A relationship between anti-replication protein A (RPA) antibodies and the ductal breast carcinoma of the proband was suggested by overexpression and aberrant localization of RPA32 in tumor cells as compared with surrounding normal ductal tissue and by the presence of anti-RPA32 antibodies before the diagnosis. The prevalence of anti-RPA32 antibodies was significantly higher (P < 0.01) among breast cancer patients (87 of 801 patients) than among noncancer controls (0 of 65 controls). Similarly, anti-RPA32 antibodies were present in 4 of 39 patients with intraductal in situ carcinoma. No associations were found between anti-RPA antibodies and survival, occurrence of a second tumor, metastases, or antibodies to p53. Reactivity to RPA32 also was detected in sera from 3 of 47 patients with other cancers.
  
  
  CONCLUSIONS
  In view of the central role of RPA in DNA replication, recombination, and repair, we suggest that autoimmunity to RPA32 may reflect molecular changes involved in the process of tumorigenesis. The finding of antibodies to RPA32 before diagnosis and their prevalence in in situ carcinoma suggest that they are potentially useful markers of early disease.
authors.affiliation: Center for Molecular Medicine and Genetics, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Tomkiel
authors.forename: H
authors.initials: H
authors.lastname: Alansari
authors.forename: N
authors.initials: N
authors.lastname: Tang
authors.forename: J B
authors.initials: JB
authors.lastname: Virgin
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: VandeVord
authors.forename: R L
authors.initials: RL
authors.lastname: Karvonen
authors.forename: J L
authors.initials: JL
authors.lastname: Granda
authors.forename: M J
authors.initials: MJ
authors.lastname: Kraut
authors.forename: J F
authors.initials: JF
authors.lastname: Ensley
authors.forename: F
authors.initials: F
authors.lastname: Fernández-Madrid
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002278:Carcinoma in Situ / Q000097:blood / Q000276:immunology / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015723:Gene Library; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009679:Nuclear Family; D012016:Reference Values; D051716:Replication Protein A; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497167:RPA1 protein, human; D051716:Replication Protein A; D016159:Tumor Suppressor Protein p53