Abstract
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). 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. 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). These results indicate the potential of autoantibody detection as a new prognostic test with possible clinical implications for the management of DCIS.
Highlights
A set of five autoantibody targets (RBP-Jk, 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 ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) transition
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 1⁄4 0.01). These results indicate the potential of autoantibody detection as a new prognostic test with possible clinical implications for the management of DCIS
In contrast to the dramatic improvement in our ability to detect ductal carcinoma in situ (DCIS), our understanding of the pathophysiology of this disease and the factors involved in its progression to invasive breast carcinoma (IBC) is limited [1]
Summary
In contrast to the dramatic improvement in our ability to detect ductal carcinoma in situ (DCIS), our understanding of the pathophysiology of this disease and the factors involved in its progression to invasive breast carcinoma (IBC) is limited [1]. Clinicohistologic features, such as a younger age, positive surgical margins, tumor size, comedo necrosis and, notably, tumor grade have consistently been correlated with DCIS recurrence. Authors' Affiliations: 1CHU Montpellier, Ho^pital Arnaud de Villeneuve, Department of Cellular Biology; and 2University of Montpellier I; Departments of 3Clinical Oncoproteomics, 4Biostatistics, 5Biology, and 6Surgery, Val d'Aurelle, Montpellier, France. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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