Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas (diagnostic/surgical samples)

Gene expression is widely used for the characterization of breast cancers. Variability due to tissue heterogeneity or measurement error or systematic change due to peri-surgical procedures can affect measurements but is poorly documented. We studied the variability of global gene expression between core-cuts of primary ER+ breast cancers and the impact of delays to tissue stabilization due to sample x-ray and of diagnostic core-cutting. Twenty-three and 56 sample pairs, respectively, were suitable for analysis. In general, there is a good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Increases in the expression of several stress/early-response genes (e.g., FOS, FOSB, JUN) were found in both studies. Substantial changes in expression of early response genes occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of diagnostic core-cut biopsy. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes. Fifty-six paired core-cuts were taken at diagnosis and 2 weeks later at surgical excision. Whole genome expression analysis was conducted on extracted RNA. Correlations and differences were assessed between the expression of individual genes, gene-sets/signatures and intrinsic subtypes.