Abstract P3-09-02: MicroRNA Expression Analysis in Lobular Neoplasia
Authors: Loudig O , Rohan T , Shapiro N , Childs G , Liu C , Wang T , Hazan R , Fineberg S. 
Published: April 2011

Background: Lobular carcinoma in situ (LCIS) is a diffuse bilateral disease and is considered a marker for increase risk for development of invasive breast cancer but there is no direct measure of risk. MicroRNAs (miRNAs), are regulators of gene expression which have shown utility as markers of diagnosis and prognosis in cancer. We studied miRNA patterns in lobular neoplasia (LN) to characterize the miRNA profile of LN and to determine if specific expression patterns of miRNA correlated with risk for progression of LCIS

Material and Methods: Formalin fixed parrafin embedded (FFPE) tumor blocks from Montefiore Hospital Bronx NY were microdissected under a light microscope prior to RNA extraction and quantification on a bioanalyzer. For profiling of miRNAs we tested our Illumina™ beadarray miRNA DASL assay with RNA extracted from 1 case of LCIS, 1 case of LCIS synchronous with invasive lobular cancer (ILC), 1 case of ILC alone and normal breast tissues as controls. We identified 41 miRNAs differentially expressed between normal and LN. We selected 8 miRNAs with the most characteristic differential expression between benign breast and LN and validated their expression in 45 FFPE breast specimens using the Taqman miRNA quantitative RT-PCR assays. The 45 cases included 9 normal breast, 10 LCIS alone, 8 LCIS from pts with synchronous ILC and the synchronous ILC and 10 ILC alone. We correlated results of miRNA profiles with type of LCIS (classic vs pleiomorphic vs LCIS with necrosis) and with development of another more significant breast cancer in pts with LCIS.

Results: The 8 miRNAs which appeared the most deregulated in LN were miR-329, miR-486, miR-375, Mir -182/183/96 cluster, miR-187 and miR-10a. The following significant correlations were observed: 1) Of 18 LCIS samples there were 3 cases of pleiomorphic LCIS (PLCIS). The highest levels of mir-375 were observed in the 3 cases of PLCIS — The average fold increase of miR-375 was 70 fold in PLCIS and the average fold increase in classic LCIS was 7.0 fold when compared to normal breast.2) Mir-182/183/96 cluster — There were 3 pts with an initial diagnosis of LCIS alone who turned out to have a more clinically significant cancer (1 with contralateral DCIS, 1 with contralateral invasive ductal cancer and ipsilateral DCIS and 1 with ipsitlateral ILC). The highest elevations of these 3 miRNAs occurred in these 3 LCIS alone pts — The average fold increase in these 3 pts for each of the three miRNAs was 55,29 and 62 respectively and the average fold increase in the other LCIS alone pts was 6,7, and 7 respectively when compared to normal breast. 3) Mir-486- This miRNA was found to be down-regulated in synchronous ILC when compare to matched LCIS (p-value 0.035).

Discussion: We provide a description of specific miRNA abnormailities observed in LN. Our results suggest that up-regulation of specific miRNAs (mir-375) may correlate with LCIS grade as well as risk for development of a more clinically significant cancer (mir-182,183 and 96). Down regulation of miRNAs (mir-486) suggest that molecular changes may be associated with cellular transitions and with progression to ILC. These preliminary results, which suggest that miRNA profiling of LCIS may help identify risk of breast cancer development, will be further investigated with a larger study

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-09-02.