Identification of a new panel of serum autoantibodies associated with the presence of in situ carcinoma of the breast in younger women.
OBJECTIVE
We examined the feasibility of using a panel of autoantibodies to multiple tumor-associated proteins as a method for early detection of breast cancer and, more particularly, carcinoma in situ (CIS).


METHODS
PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens by proteomic approaches. The seroreactivity of a panel of antibodies consisting of these three antigens and two previously described autoantigens, HSP60 and MUC1, was tested on 235 samples (60 from primary breast cancer patients, 82 from CIS patients, and 93 from healthy controls) with the use of specific ELISAs. FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by reverse transcription-PCR and immunohistochemistry in early-stage breast tumors.


RESULTS
Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls. When combined, the five markers significantly discriminated primary breast cancer [receiver operating characteristic area under the curve, 0.73; 95% confidence interval (95% CI), 0.60-0.79] and CIS (receiver operating characteristic area under the curve, 0.80; 95% CI, 0.71-0.85) from healthy individuals. Importantly, the receiver operating characteristic-area under the curve value of the autoantibody panel was able to distinguish CIS, including high grades, from healthy controls in women under the age of 50 years (receiver operating characteristic area under the curve, 0.85; 95% CI, 0.61-0.92). Finally, only FKBP52 mRNA and protein levels were found to be increased in CIS and primary breast cancer compared with healthy breast tissue.


CONCLUSIONS
This autoantibody assay against a panel of five antigens allows for an accurate discrimination between early-stage breast cancer, especially CIS, and healthy individuals. These results could be of interest in detecting early breast cancer as an aid to mammography, especially in women under the age of 50 years with aggressive cancers.
Desmetz
Caroline
C
Department of Cellular Biology, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier 34000, France.
Bascoul-Mollevi
Caroline
C
Rochaix
Philippe
P
Lamy
Pierre-Jean
PJ
Kramar
Andrew
A
Rouanet
Philippe
P
Maudelonde
Thierry
T
Mangé
Alain
A
Solassol
Jerome
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D002278:Carcinoma in Situ / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology; D021984:Cyclophilin A / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003937:Diagnosis, Differential; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology; D054464:Peroxiredoxins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D018834:Chaperonin 60; C060192:MUC1 protein, human; D018396:Mucin-1; C086065:PRDX2 protein, human; D054464:Peroxiredoxins; D021984:Cyclophilin A; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4