Detection and diagnosis

ABSTRACT Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. Overexpression of several genes may be a result of surgical trauma or preoperative manipulation, such as the injection of radioactive substance to examine spread of cancer cells (sentinel node), and may not reflect any biological impact of the disease. In this study we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Fifteen patients were included of which 12 had undergone sentinel node diagnosis procedure before operation. Gene expression and miRNA microarray analysis were performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun cancer. Only two miRNAs, miR-923 and miR-1274b, were differentially expressed. These results were confirmed by large-scale expression signature analysis, which showed stability of most breast cancer specific expression signatures, while signatures related to immune response and stress response scored differently on pre- and postoperative samples. The expression profiles of preoperative breast cancer tumors differ from those of postoperative tumors for a small fraction of genes (228 out of approx. 18 000). However, the expression of these genes in concert affects specific biological pathways, which may relate to stress responses in the tissue. The results highlight the necessity of having in mind that some of the expression profiles found in the analyses of breast cancer tissue may simply be result of differences in the surgical trauma and timing of when samples are taken, and not necessarily associated with tumor biology. Disclosure All authors have declared no conflicts of interest.