LAUSR

Background: Ductal carcinoma in situ (DCIS) comprises 20-25% of screen-detected breast cancer and, like invasive ductal carcinoma (IDC), is heterogeneous in terms of underlying biology, presentation and outcome. There are limited potential biomarkers of outcome for DCIS, although estrogen receptor (ER)-positive (pos), progesterone receptor (PgR)-pos, and HER2-negative (neg) DCIS appears to have a better outlook than DCIS neg for ER and PgR but pos for HER2. The aim of this study was to identify markers for DCIS to develop a panel to stratify DCIS into DCIS at low or high risk of further DCIS. Methods and results: To identify genes driving DCIS evolution followed by the progression to IDC, we first used transcriptional data sets (GSE788, GSE16873) which had data from both normal mammary glands (NMG) and DCIS and performed class comparison (NMG vs DCIS). For both GSE7882 and GSE16883, the number of over- and under-expressed genes was 297 and 187. Over-expressed genes in DCIS represented a mitotic/proliferative feature annotated as mitotic spindle and condensed chromosome. Under-expressed genes represented loss of epithelial features annotated as epithelial cell differentiation and development. A total of 484 differentially expressed genes in DCIS were further correlated with recurrence events of IDC using Kessler9s breast cancer data set to identify genes contributing aggressive feature across DCIS and IDC. Genes correlating to recurrence events were selected. From 484 genes, 99 were significantly associated with recurrence events of IDC (with P Conclusion: SOX11 is exclusively overexpressed in ER/PgR-neg DCIS and is a candidate clinical marker for recurrence of DCIS or progression of ER/PgR-neg DCIS to IDC. Citation Format: Kazuharu Kai, Wei Lu, Fei Yang, Ximing Tang, Ignacio I. Wistuba, Subrata Sen, Alastair Thompson. SOX11 is a potential clinical marker for hormone receptor negative ductal carcinoma in situ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 634.