Comprehensive Gene Expression Analysis Identifies Molecular Markers Involved With The Progression Of Ductal Carcinoma In Situ Of The Breast

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous entity with diverse clinical and molecular manifestations. Although the majority of the patients shows excellent outcome, a few of them experience progression to invasive disease. The identification the earliest molecular alterations that are crucial for the acquisition of the invasive capability of the epithelial tumor cells may contribute to a better understanding of the DCIS progression and, more importantly, can lead to the development of molecular markers for distinguishing patients that would benefit from minimal therapeutic interventions from patients that require the traditional multidisciplinary approaches. In this sense, we conducted a comprehensive gene expression profiling of in situ ductal carcinoma by comparing epithelial cells from pure DCIS (9 samples) and from in situ component of an invasive breast carcinoma lesion (17 samples). In order to asses gene expression differences we combined laser capture microdissection with two custom cDNA microarray approaches, a 4.8K platform consisting of 4,608 human genes and a 2.3K platform containing 390 genes belonging to WNT, P13K signaling pathways and EMT process (Epithelial-mesenchymal transition). We identified 89 differently expressed genes between pure DCIS and DCIS component of IBC lesions considering both platforms, the majority of them being up-regulated in pure DCIS lesions (83 genes). From this set of 89 genes, 22 were confirmed as differently expressed in a partial independent cohort by RT-qPCR assays. Interestingly all of them were up regulated in pure DCIS. Based on the expression profile of the 22 validated genes we were able to discriminate 100% of the samples from DCIS component of IBC tumors from 80% of the pure DCIS samples, by unsupervised hierarchical clustering, suggesting that these genes are potential molecular markers for predicting progression of pure DCIS. Finally, considering Ingenuity pathway analysis of this 22 genes, we suggest that genes involved with Cell-to-cell signaling and interaction, cell morphology and carbohydrate metabolism are downregulated during DCIS progression. In conclusion, in this work we have identified promising molecular markers that could improve the identification of patients diagnosed with pure DCIS at a higher risk of progression to the invasive disease. Citation Format: Elisa N. Ferreira, Eliana V. Elias, Nadia Castro, Paulo Pineda, Cynthia Osorio, Mabel P. Fernandez, Sabrina D. Silva, Maria do Socorro Maciel, Fernando A. Soares, Dirce M. Carraro. Comprehensive gene expression analysis identifies molecular markers involved with the progression of ductal carcinoma in situ of the breast. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 452. doi:10.1158/1538-7445.AM2014-452