Project description:The identification of lobular caricnoma in situ (LCIS) in a patient's specimen confers and appreciable increased risk of development of future invasive mammary carcinoma. However the study of LCIS presents a challenge as it is usually only recognized in fixed specimens and no good in vivo or in vitro models currently exist. Recent advances in high throughput genomics have made possible comprehensive copy number analysis of lesions such as this. We have characterized LCIS on microdissected cases of archival patient samples using aCGH. We used 4 cases of LCIS with adjacent ILC. Histological sections from 4 cases of LCIS and 4 cases of ILC microdissected, DNA extracted and subjected to whole genome amplification, and aCGH.
Project description:Invasive lobular carcinoma (ILC) of the breast accounts for 5-15% of breast cancers and is characterized by loss of E-cadherin and believed to arise via a linear histological progression. Genomic studies have identified a clonal relationship between ILC and concurrent lobular carcinoma in situ (LCIS) lesions, suggesting that LCIS may be a precursor lesion. It has been shown that an LCIS diagnosis confers a 15-20% risk of progression to ILC, over a lifetime. Currently no molecular test or markers can identify LCIS lesions likely to progress to ILC. Since microRNA (miRNA) expression changes have been detected in a number of other cancer types, we explored whether their dysregulation might be detected during progression from LCIS to ILC. Using the Illumina miRNA profiling platform, designed for simultaneous analysis of 470 mature miRNAs, we analyzed the profiles of archived normal breast epithelium, LCIS lesions found alone, LCIS lesions concurrent with ILC, and the concurrent ILCs, as a model of linear histological progression toward ILC. We identified two sets of differentially expressed miRNAs, the first set highly expressed in normal epithelium, including hsa-miR-224, -139, -10b, -450, 140 and -365 and the second set upregulated during lobular neoplasia, including hsa-miR-375, -203, -425-5p, -183, -565 and -182. Using quantitative RT-PCR, we validated a trend of increased expression for hsa-mir-375, hsa-mir-182, and hsa-mir-183 correlating with ILC progression. As we detected increased expression of hsa-miR-375 in LCIS lesions synchronous with ILC, we sought to determine whether hsa-mir-375 might induce phenotypes reminiscent of lobular neoplasia by expressing it in the MCF10A 3D culture model of mammary acinar morphogenesis. Increased expression of hsa-miR-375 resulted in loss of cellular organization and acquisition of a hyperplastic phenotype. These data suggest that dysregulated miRNA expression contributes to lobular neoplastic progression. 6 specimens were analyzed in duplicate. One frozen normal lobular epithelium and the matched FFPE (1 month old) normal lobular epithelium. One lobular carcinoma in situ (LCIS) found alone, one LCIS synchronous with an invasive lobular carcinoma (ILC), the synchronous ILC (from a different archived block), and one ILC found alone without presence of any other breast cancer.
Project description:The identification of lobular caricnoma in situ (LCIS) in a patient's specimen confers and appreciable increased risk of development of future invasive mammary carcinoma. However the study of LCIS presents a challenge as it is usually only recognized in fixed specimens and no good in vivo or in vitro models currently exist. Recent advances in high throughput genomics have made possible comprehensive copy number analysis of lesions such as this. We have characterized LCIS on microdissected cases of archival patient samples using aCGH. We used 4 cases of LCIS with adjacent ILC.
Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines
Project description:Analysis of invasive lobular carcinoma (ILC) at gene expression level. Samples are annotated with breast cancer specific survival (BCSS) and tumour grade. Results are part of a larger study about molecular signatures that are associated with distinct clinical outcomes in ILC.
Project description:We identified MDC1 as a putative novel transcriptional co-regulator of estrogen receptor alpha (ER) in models of invasive lobular carcinoma. In this study, our goal was to define the contribution of MDC1 to regulation of the ER transcriptome in ILC cell lines versus invasive ductal carcinoma cells.
Project description:Invasive lobular carcinoma (ILC) is the second most frequent histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for 5-15% of all breast cancers. Although clinical outcomes of ILC and IDC seem similar, the molecular processes underlying ILC are still largely unknown. To explore this, we have performed a comprehensive proteomics analysis of a large ILC patient cohort. These data are generated in the context of the RATHER consortium (http://www.ratherproject.com/)
Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray.
Project description:cDNA aCGH study of pure DCIS (breast duct carcinoma in situ) without invasive tumor, DCIS associated with IDC (breast invasive duct carcinoma) and its IDC component 23 patients: 6 pure DCIS without invasive cancer and no history of invasive cancer, 17 DCIS associated with IDC. Out of the latter 1 tumor had only enough DCIS (#16) for aCGH and one - IDC (#23) Keywords: Comparative clinical study