Abstract
IntroductionThe role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression in histologically normal tissue adjacent to breast tumor, if this is influenced by the tumor, and how this compares with non-tumor-bearing breast tissue.MethodsTo address this, we have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty (n = 44).ResultsBased on this data, we determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumor-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumor tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favorable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis.ConclusionOur data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression dataset for comparative studies of tumor expression profiles.
Highlights
The role of the cellular microenvironment in breast tumorigenesis has become an important research area
Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression dataset for comparative studies of tumor expression profiles
Identification of stroma- and epithelium-specific gene expression profiles To determine the gene expression profiles of morphologically normal epithelium and stroma derived from reduction mammoplasties and breast cancer tissue, we integrated the use of Laser capture microdissection (LCM) and T7-based RNA amplification with DNA microarrays
Summary
The role of the cellular microenvironment in breast tumorigenesis has become an important research area. Breast cancer and other malignancies and, because of their genome-wide nature, they allow for the identification of gene expression changes that have occurred between normal and tumor breast tissues. Using these approaches, several studies have successfully identified breast cancer subtypes and prognostic markers; the utility of such markers in the clinic remains open [7,8,9,10,11]. The presence of loss of heterozygosity in normal stromal breast tissue adjacent to, and distant from, the tumor site has been demonstrated, suggesting that changes in stroma may have occurred [13]. Since surgery is the standard of care, normal cells harboring alterations that may be relevant to cancer progression may remain and, could have important clinical implications
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
