Biological and prognostic associations of miR-205 and let-7b in breast cancer revealed by in situ hybridization analysis of micro-RNA expression in arrays of archival tumour tissue

Authors

  • John Le Quesne,

    Corresponding author
    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    • Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
    Search for more papers by this author
  • Julia Jones,

    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    Search for more papers by this author
  • Joanna Warren,

    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    Search for more papers by this author
  • Sarah-Jane Dawson,

    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    Search for more papers by this author
  • H Raza Ali,

    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    Search for more papers by this author
  • Helen Bardwell,

    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    Search for more papers by this author
  • Fiona Blows,

    1. Department of Oncology, Strangeways Research Laboratories, University of Cambridge, UK
    Search for more papers by this author
  • Paul Pharoah,

    1. Department of Oncology, Strangeways Research Laboratories, University of Cambridge, UK
    2. Cambridge Experimental Cancer Medicine Centre (ECMC) and NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals, UK
    Search for more papers by this author
  • Carlos Caldas

    1. Cancer Research UK, Cambridge Research Institute and Department of Oncology, University of Cambridge, UK
    2. Cambridge Experimental Cancer Medicine Centre (ECMC) and NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals, UK
    Search for more papers by this author

  • No conflicts of interest were declared.

Abstract

Micro-RNAs (miRNAs) are frequently dysregulated in a range of human malignancies, many have been shown to act either as tumour supressors or oncogenes and several have been implicated in breast cancer. However, breast cancer is a diverse disease and little is known about the relationships between miRNA expression, clinical outcome and tumour subtype. We used locked nucleic acid probe in situ hybridization (LNA-ISH) to visualize, in tissue micro-arrays (TMAs) of 2919 formalin-fixed paraffin-embedded (FFPE) archival breast tumours, the expression of two key miRNAs that are frequently lost in a range of solid malignancies, let-7b and miR-205. These miRNAs were also quantified by quantitative reverse transcription PCR in cores of FFPE tissue from 40 of these cases, demonstrating that LNA-ISH is semi-quantitative. The tumours in the TMAs were assigned to subtypes based on their immunohistochemical (IHC) staining with ER, PR, HER2, CK5/6 and EGFR. let-7b expression was shown to be associated with luminal tumours and to have an independent significant positive prognostic value in this group. miR-205 is associated with tumours of ductal morphology and is of significant positive prognostic value within these tumours. We propose that the expression of miR-205 may contribute to ductal tumour morphology. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Ancillary