Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression

Vargas, Ana Cristina, McCart Reed, Amy E., Waddell, Nic, Lane, Annette, Reid, Lynne E., Smart, Chanel E., Cocciardi, Sibylle, da Silva, Leonard, Song, Sarah, Chenevix-Trench, Georgia, Simpson Peter T. and Lakhani, Sunil R. (2012) Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression. Breast Cancer Research and Treatment, 135 1: 153-165.

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Author Vargas, Ana Cristina
McCart Reed, Amy E.
Waddell, Nic
Lane, Annette
Reid, Lynne E.
Smart, Chanel E.
Cocciardi, Sibylle
da Silva, Leonard
Song, Sarah
Chenevix-Trench, Georgia
Simpson Peter T.
Lakhani, Sunil R.
Title Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression
Journal name Breast Cancer Research and Treatment   Check publisher's open access policy
ISSN 0167-6806
1573-7217
Publication date 2012
Sub-type Article (original research)
DOI 10.1007/s10549-012-2123-4
Volume 135
Issue 1
Start page 153
End page 165
Total pages 13
Place of publication New York, United States
Publisher Springer
Collection year 2013
Language eng
Formatted abstract The progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) marks a critical step in the evolution of breast cancer. There is some evidence to suggest that dynamic interactions between the neoplastic cells and the tumour microenvironment play an important role. Using the whole-genome cDNA-mediated annealing, selection, extension and ligation assay (WG-DASL, Illumina), we performed gene expression profiling on 87 formalin-fixed paraffin-embedded (FFPE) samples from 17 patients consisting of matched IDC, DCIS and three types of stroma: IDC-S (<3 mm from IDC), DCIS-S (<3 mm from DCIS) and breast cancer associated-normal stroma (BC-NS; >10 mm from IDC or DCIS). Differential gene expression analysis was validated by quantitative real time-PCR, immunohistochemistry and immunofluorescence. The expression of several genes was down-regulated in stroma from cancer patients relative to normal stroma from reduction mammoplasties. In contrast, neoplastic epithelium underwent more gene expression changes during progression, including down regulation of SFRP1. In particular, we observed that molecules related to extracellular matrix (ECM) remodelling (e.g. COL11A1, COL5A2 and MMP13) were differentially expressed between DCIS and IDC. COL11A1 was overexpressed in IDC relative to DCIS and was expressed by both the epithelial and stromal compartments but was enriched in invading neoplastic epithelial cells. The contributions of both the epithelial and stromal compartments to the clinically important scenario of progression from DCIS to IDC. Gene expression profiles, we identified differential expression of genes related to ECM remodelling, and specifically the elevated expression of genes such as COL11A1, COL5A2 and MMP13 in epithelial cells of IDC. We propose that these expression changes could be involved in facilitating the transition from in situ disease to invasive cancer and may thus mark a critical point in disease development.
Keyword Invasive ductal carcinoma
Ductal carcinoma in situ
Tumour stroma
Formalin fixed paraffin embedded tissue
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 21 June 2012

 
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Created: Thu, 12 Jul 2012, 17:42:01 EST by Dr Sarah Song on behalf of Institute for Molecular Bioscience