Serum autoantibody signature of ductal carcinoma in situ progression to invasive breast cancer.
OBJECTIVE
The identification of markers associated with progression to invasive breast cancer (IBC) is a major factor that can guide physicians in the initial therapeutic decision and the management of ductal carcinoma in situ (DCIS).


METHODS
We examined autoantibody targets in 20 DCIS and 20 IBC patients using protein microarrays and identified humoral responses that can be used to distinguish the two groups. The five most differentially targeted antigens were selected to generate an autoantibody signature for the in situ to invasive breast cancer transition. This signature was next tested on 120 independent samples (61 DCIS and 59 IBC) using specific ELISA assays. The prognosis value of the autoantibody signature was finally evaluated in a cohort of DCIS patients followed for 5 years.


RESULTS
A set of five autoantibody targets (RBP-Jκ, HMGN1, PSRC1, CIRBP, and ECHDC1) with the highest differential signal intensity found in the protein microarrays experiment was used to establish an autoantibody signature of the DCIS to IBC transition. Using ELISA, this signature significantly discriminated DCIS from IBC [area under the ROC curve (AUC) = 0.794, 95% confidence interval (CI): 0.674-0.877]. Interestingly, our panel could highly distinguish low-grade DCIS from high-grade DCIS exhibiting an AUC of 0.749 (95% CI: 0.581-0.866). Finally, using a Kaplan-Meier analysis, the autoantibody signature could significantly divide the DCIS patients into a poor prognosis group and a good prognosis group (P = 0.01).


CONCLUSIONS
These results indicate the potential of autoantibody detection as a new prognostic test with possible clinical implications for the management of DCIS.
Departement de Biologie Cellulaire, 371 Avenue du Doyen Giraud, 34295 Montpellier Cedex 5, France.
Alain
A
Mangé
Jérôme
J
Lacombe
Caroline
C
Bascoul-Mollevi
Marta
M
Jarlier
Pierre-Jean
PJ
Lamy
Philippe
P
Rouanet
Thierry
T
Maudelonde
Jérôme
J
Solassol
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000097:blood / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024241:HMGN1 Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D043586:Methylmalonyl-CoA Decarboxylase / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; C491390:CIRBP protein, human; D024241:HMGN1 Protein; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C485740:PSRC1 protein, human; D010750:Phosphoproteins; C497570:RBPJ protein, human; D016601:RNA-Binding Proteins; D043586:Methylmalonyl-CoA Decarboxylase