Abstract 2733: Molecular markers for predicting progression of pure ductal carcinoma in situ of the breast

Abstract

Abstract INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of tumors which has an uncertain and poorly understood evolution. For this reason, the identification of molecular factors necessary for progression to invasive disease is one of the main concerns of the scientific community. We previously identified, by a microarray assay, a group of genes potentially involved in progression of DCIS, which are differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma (DCIS-IDC). For this experiment, only the in situ components of pure DCIS and DCIS-IDC lesions were isolated using laser microdissection technique. AIM: Seek novel molecular markers to predict invasiveness potential in a DCIS group of breast carcinomas by qRT-PCR and Immunohistochemistry (IHC). METHODS: For qRT-PCR, 18 genes were selected, for which there were available antibodies. The qRT-PCR reactions were performed in ABIPrism 7700 Sequence Detection System (Applied Biosystems, Foster City, CA, USA) and the criterion of gene expression difference was equal or greater than 2-fold change. IHC was performed in a tissue microarray (TMA), using a biotin-free polymeric system for visualization (Flex+, DAKOTM). The distribution of IHC markers was analyzed using the Chi-square test for trend or Fisher's exact test. RESULTS: The expression of 4 genes (ADFP, ARHGAP19, ANAPC13 and CLTCL1) was confirmed by qRT-PCR, in the initial sample set used in the microarray experiment, presenting higher expression in the pure DCIS group. IHC was conducted to evaluate the corresponding proteins, using an independent group of 47 pure DCIS and 35 DCIS-IDC samples arrayed in TMA. Two genes, ANAPC13 (p=0.0379) and CLCTL1 (p=0.0471), confirmed the expression at protein level, showing significant higher cytoplasm staining in the pure DCIS group. CONCLUSION: ANAPC13 and CLTCL1 may be involved in progression of DCIS, being good candidates for predicting invasion of pure DCIS. Financial support: CEPID and FAPESP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2733.