Comparison of Gene Expression Profiles of Areas of Micropapillary (MP) Differentiation of Invasive Breast Carcinomas with Focal MP features with Usual Ductal (No Special Type, NST) Components
MJ Wagoner, G Paragh, Z Rakosy, M Ghayouri, G Acs. University of South Florida College of Medicine, Tampa, FL; Moffitt Cancer Center, Tampa, FL
Background: Invasive breast carcinomas with MP features are aggressive tumors frequently associated with lymphatic invasion and nodal metastasis. Although areas of MP differentiation may be very focal within breast cancers, metastatic tumor foci often show similar morphologic features in these cases, suggesting that they arise from these limited areas. We hypothesized that comparison of the gene expression profiles of MP areas to NST components of the same tumors may help identify genes that play a significant role in lymphatic tumor spread.
Design: MP and NST areas of 16 archived formalin-fixed paraffin-embedded (FFPE) invasive breast carcinomas with focal MP features were macrodissected separately and RNA was isolated after DNase digestion. Sample quality was assessed by RLP13a ribosomal protein mRNA specific TaqMan quantitative real time PCR (q-RT-PCR) after reverse transcription. The 12 highest quality sample pairs were subjected to whole genome gene expression analysis using Illumina's cDNA-mediated annealing, selection, extension and ligation (DASL) assay based bead arrays, which are specifically designed to allow expression analysis of more than 24,000 human genes from partially degraded RNA from FFPE tissues. In addition, 13 genes with known involvement in breast cancer pathogenesis were also quantified by TaqMan q-RT-PCR in the same samples.
Results: Areas of MP features ranged between 5 to 50% in the tumors. Comparison of whole genome gene expression profiles of MP versus NST areas of the tumors revealed 25 differentially expressed genes at a significance level of p<0.001. Among the 13 genes evaluated separately by TaqMan q-RT-PCR, we identified Tenascin C, a matrix protein involved in metastasis, to be expressed differentially between MP and NST areas of the tumors. Verification of whole genome DASL and TaqMan results are being carried out by immunohistochemistry.
Conclusions: Our results suggest that focal areas of MP differentiation in invasive breast carcinomas show differences in their gene expression profiles compared to NST areas of the same tumors. Identification of differentially expressed genes in MP areas may help identify genes and/or proteins that play a significant role in the metastatic spread of these aggressive tumors.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 53, Monday Morning