Unknown,Transcriptomics,Genomics,Proteomics

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Gene profiling using archival formalin-fixed paraffin-embedded breast cancer specimens can generate informative microarray data: A comparison with matched fresh fine needle aspiration biopsy samples (FNA samples)

ABSTRACT: The Formalin-Fixed Paraffin-Embedded (FFPE) samples on selected breast cancer subtypes (ER+/Her2-, ER+/Her2+, ER-/Her2+, and ER-/Her2-) and their paired fresh fine needle aspirated biopsies (FNA) were investigated. The cases represented different subtypes of breast cancers based on their clinical receptors ER (E) and Her2 (H) status to demonstrate the ability of gene profiles to differentiate these tumors. Compared to FNA specimens, FFPE samples yielded relatively more degraded RNA, and 80% of the samples deemed suitable for cDNA-mediated annealing, selection, extension and ligation (DASL) assay. It is able to demonstrate that gene profiles from FFPE microarrays were reproducible and correlated well with the corresponding gene profiles from FNA microarrays. The gene profiles from both FNA and FFPE could differentiate the four breast cancer subtypes, and the expression levels of corresponding gene set were consistent with qRT-PCR and correlated to the clinical outcomes on published microarray data. It supports the use of FFPE specimens to develop a prognostic tool for breast cancers which can obviate the need for fresh specimens. 25 FNA specimens were processed for direct hybridization assays using Illumina Human-Ref8 version 3 BeadChips. Invasive ductal carcinoma (IDC)-type subtypes ER+/Her2-, ER+/Her2+, ER-/Her2+, and ER-/Her2- (ER: estrogen receptor, HER2: human epidermal growth factor receptor 2) were analyzed.

ORGANISM(S): Homo sapiens

SUBMITTER: Dong-Yu Wang

PROVIDER: E-GEOD-23385 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens.

Sadi Al Muktafi AM Wang Dong-Yu DY Youngson Bruce J BJ Miller Naomi N Boerner Scott S Done Susan J SJ Leong Wey L WL

BMC cancer 20110616

<h4>Background</h4>The ability of gene profiling to predict treatment response and prognosis in breast cancers has been demonstrated in many studies using DNA microarray analyses on RNA from fresh frozen tumor specimens. In certain clinical and research situations, performing such analyses on archival formalin fixed paraffin-embedded (FFPE) surgical specimens would be advantageous as large libraries of such specimens with long-term follow-up data are widely available. However, FFPE tissue proces ...[more]

PMID: 21679412

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Project description:Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2-neu) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+. We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER+ cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs may contribute to the more invasive properties and unfavorable prognosis of Her2+ breast cancer. These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer. We isolated CAFs from twenty primary breast cancer samples representing three main subtypes (ER+ (n=7), TNBC (n=7), Her2+ (n=6)) and performed gene expression profile analyses on RNA isolated from these early passage CAFs. Those samples were done in two batches with 4 samples repeated in both batches. One TNBC sample was found to be an outlier and not used in the analysis.

Dataset Information

Gene profiling using archival formalin-fixed paraffin-embedded breast cancer specimens can generate informative microarray data: A comparison with matched fresh fine needle aspiration biopsy samples (FNA samples)

Publications

Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens.

Similar Datasets

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