Abstract P4-06-11: Gene Expression Profiling Identifies Potential Precursor Genes in Lobular Carcinoma In Situ

INTRODUCTION: Historically lobular carcinoma in situ (LCIS) has been considered a risk marker but not a true precursor of invasive breast cancer. Emerging evidence of clonal relatedness between LCIS and synchronous invasive lobular cancers (ILC) has reopened this debate. We hypothesized that gene expression profiling of LCIS and synchronous ILC could identify genes that confer precursor potential in LCIS. METHODS: Patients with LCIS +/− ILC undergoing mastectomy were prospectively identified. Mastectomies were sampled to collect fresh frozen normal epithelium (N), LCIS and ILC. Laser Capture Microdissection was used to isolate purify cell populations and total mRNA was subject to Affymetrix HU133 2.0 gene expression array. Transcript abundance was compared across samples in a paired analysis (P RESULTS: Patient matched triplets (N, LCIS, ILC) were available from 23 mastectomies. 206 probe sets (178 genes) fit the PPG definition, 154 probe sets (130 genes) displayed monotonically decreasing expression and 52 probe sets (48 genes) displayed monotonically increasing expression. The table shows the top five cellular functions and canonical pathways related to the (PPG). The candidates PPGs are distributed across all chromosomes, with the highest frequencies on 1 q (9.6%), 16q (7.3%), 2q (5.06%), 5q (5.06%) and 4q (4.49%). All 13 potential precursor genes identified on 16q and the 9 PPG identified on 5q showed monotonically decreasing expression while 13/17 PPGs identified on 1q showed monotonically increasing expression. Among all upregulated PPG, 27.1% are located at 1q while 10% of all downregulated PPGs are located at 16q. CONCLUSIONS: Gene expression profiling identified 178 candidate genes with monotonically increasing or monotonically decreasing expression across patient matched samples of N-LCIS-ILC. Top cellular functions and canonical pathways represented by the candidate genes are known to be associated with carcinogenesis, suggesting that dysregulation of these candidate genes may confer precursor potential in LCIS. The abundance of potential precursor genes on chromosomes 1 q and 16q is also consistent with the model of lobular carcinogenesis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-11.