Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas

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  • López-Knowles, Elena
    • Other Affiliation: Royal Marsden Hospital, London, UK; Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK
  • Gao, Qiong
    • Other Affiliation: Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK
  • Cheang, Maggie C U
    • Other Affiliation: Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
  • Morden, James
    • Other Affiliation: Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
  • Parker, Joel
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Martin, Lesley-Ann
    • Other Affiliation: Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK
  • Pinhel, Isabel
    • Other Affiliation: Royal Marsden Hospital, London, UK; Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK; Present address: Kingston University, London, UK
  • McNeill, Fiona
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Hills, Margaret
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Detre, Simone
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Afentakis, Maria
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Zabaglo, Lila
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Dodson, Andrew
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Skene, Anthony
    • Other Affiliation: Royal Bournemouth Hospital, Bournemouth, UK
  • Holcombe, Chris
    • Other Affiliation: Royal Liverpool University Hospital, Liverpool, UK
  • Robertson, John
    • Other Affiliation: Faculty of Medicine & Health Sciences, Queen’s Medical Centre, Nottingham, UK
  • Smith, Ian
    • Other Affiliation: Royal Marsden Hospital, London, UK
  • Bliss, Judith M
    • Other Affiliation: Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK
  • Dowsett, Mitch
    • Other Affiliation: Royal Marsden Hospital, London, UK; Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK
Abstract
  • Abstract Background Gene expression is widely used for the characterisation 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 stabilisation due to sample X-ray and of diagnostic core cutting. Methods Twenty-six paired core-cuts were taken immediately after tumour excision and up to 90 minutes delay due to sample X-ray; 57 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. Results Twenty-three and 56 sample pairs, respectively, were suitable for analysis. The range of correlations for both sample sets were similar with the majority being >0.97 in both. Correlations between pairs for 18 commonly studied genes were also similar between the studies and mainly with Pearson correlation coefficients >0.6 except for a small number of genes, which had a narrow-dynamic range (e.g. MKI67, SNAI2). There was no systematic difference in intrinsic subtyping between the first and second sample of either set but there was c.15 % discordance between the subtype assignments between the pairs, mainly where the subtyping of individual samples was less certain. Increases in the expression of several stress/early-response genes (e.g. FOS, FOSB, JUN) were found in both studies and confirmed findings in earlier smaller studies. Increased expression of IL6, IGFBP2 and MYC (by 17 %, 14 % and 44 %, respectively) occurred between the samples taken 2 weeks apart and again confirmed findings from an earlier study. Conclusions There is generally good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes. 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. Trial registration Trial number CRUK/07/015 . Study start date September 2008.
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  • Article
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  • In Copyright
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  • López-Knowles et al.
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  • English
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  • Breast Cancer Research. 2016 Apr 01;18(1):39
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  • BioMed Central

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