Abstract P3-17-02: Gene expression differences between ductal carcinoma in situ with and without progression to invasive breast cancer

Abstract

Abstract Background The mechanism behind progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC) remains unknown. The aim of our study was to increase our understanding regarding molecular alterations driving DCIS progression by comparing gene-expression patterns between patients with pure DCIS and patients with synchronous DCIS and IBC. Methods In this retrospective study, we included patients with extensive pure DCIS (n=12), defined as > 5 cm, as a representation of biologically indolent lesions with limited invasive capacity. These cases were matched with patients with a limited DCIS component, defined as < 1 cm, and synchronous IBC (n=12), representing lesions with a high invasive potential. Matching was based on age and surrogate DCIS subtypes. Gene expression profiling, using 93 tumor-specific target genes, was performed to identify transcriptional differences between the DCIS components of these two groups. The identified genes were validated by immunohistochemistry. Results In total, for 9 genes there was a significant difference in gene expression between patients with pure DCIS and patients with DCIS and synchronous IBC. The majority of these 9 genes were significantly higher expressed in DCIS samples with IBC, including PLAU (P=0.002), COL1A1 (P=0.006), KRT81 (P=0.009), S100A7 (P=0.015), SCGB1D2 (P=0.023), KRT18 (P=0.029) and NOTCH3 (P= 0.044), while EGFR and CXCL14 showed a significantly higher expression in pure DCIS (P=0.015 and P=0.028 respectively). Based on these 9 genes, unsupervised hierarchical clustering-analysis revealed distinct clustering of patients with pure DCIS and patients with DCIS and synchronous IBC. Immunohistochemical analyses are in progress. Conclusion This pilot study suggests that patients with pure DCIS have a significant different gene expression pattern as compared to patients with DCIS and synchronous IBC. If these results can be validated in an independent cohort, these differently expressed genes could be used to predict progression in individual patients diagnosed with DCIS. Furthermore, these genes may pinpoint driver pathway(s) that play an important role in the progression of DCIS to IBC. Citation Format: Doebar SC, Sieuwerts AM, de Weerd V, Martens JWM, van Deurzen CHM. Gene expression differences between ductal carcinoma in situ with and without progression to invasive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-17-02.