Molecular Pathology: SY18-1 MOLECULAR PROFILING OF BREAST DUCTAL CARCINOMA IN-SITU.

Ductal carcinoma in-situ (DCIS) is a precursor of invasive breast carcinoma (IBC) and highly heterogeneous with variable presentation, morphology, and behavior. Although significant advance has been made in understanding the molecular changes in IBC in the past decade, the exact molecular behavior of DCIS, especially how it progresses to IBC is not well understood. Biomarkers that predict development of IBC are needed to improve personalized therapy. We have shown HER2 positivity in DCIS is significantly predictive of co-existent early IBC, raising a hypothesis that there are significant, differentially expressed genes in HER2 positive DCIS that are associated with high risk of developing IBC, as compared to more indolent DCIS. Gene expression profiles were performed in high nuclear grade DCIS, with different receptor status, using Affymetrix Human Gene 1.0 ST array and analyzed with the MATLAB software. Approximately thirty genes were identified to be expressed differently in the HER2 subtype as compared to the two other groups (ER/PR+ and triple negative). Uncovering gene expression signatures of HER2 positive DCIS can enhance our understanding of the mechanisms of breast cancer progression and become the basis for developing new predictive biomarkers and/or therapeutic targets, enhancing the management of patients with DCIS.