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PLK1 and YY1 interaction in follicular lymphoma is associated with unfavourable outcome
  1. Harriet E Sandison1,
  2. Suzanne Usher2,
  3. Ehsan G Karimiani2,
  4. Garry Ashton3,
  5. Lia P Menasce4,
  6. John A Radford2,
  7. Kim Linton2,
  8. Richard J Byers2,5
  1. 1The Medical School, The University of Manchester, Manchester, Greater Manchester, UK
  2. 2Faculty of Medical and Human Sciences, Institute of Cancer Sciences, The University of Manchester, Manchester, Greater Manchester, UK
  3. 3The Histology Unit, Paterson Institute for Cancer Research, The University of Manchester, Greater Manchester, Manchester, UK
  4. 4Department of Histopathology, The Christie NHS Foundation Trust, Manchester, Greater Manchester, UK
  5. 5Manchester Academic Health Science Centre, Manchester, Greater Manchester, UK
  1. Correspondence to Dr R J Byers, Department of Histopathology, Manchester Royal Infirmary, Oxford Road, Manchester, Greater Manchester M13 9WL, UK; richard.byers{at}cmft.nhs.uk, r.byers{at}manchester.ac.uk

Abstract

Aims Ying Yang 1 (YY1) is a transcription factor involved in both proliferation and apoptosis. It is prognostic in follicular lymphoma (FL), increased protein levels being associated with favourable outcome. PLK1 is a critical regulator of mitosis, playing a role in spindle formation and in regulation of the G2/M cell cycle checkpoint. PLK1 phosphorylates YY1 at the G2/M checkpoint with activation of YY1 and resultant progression from G2 into mitosis.

Methods This study aims to investigate possible molecular coexpression and interaction of YY1 with PLK1 in FL using Duolink II in situ proximity ligation assay (PLA) in 51 FL samples in a tissue microarray.

Results Positive PLA signals were present at variable frequency and Kaplan-Meier analysis showed association of signal frequency above the median with unfavourable outcome (p=0.0270). PLA signals were localised to the nuclear edge, with only one signal per cell, suggesting PLK1 and YY1 coexpression at the centrosome. In a minority of cells, two very close PLA signals were present in a single cell, and occasionally, there was a strong ring of semi-confluent fluorescent PLA signals round the nucleus of non-dividing cells, while rarely events were observed in the cytoplasm surrounding dividing cells.

Conclusions The results confirm association of YY1 and PLK1 with outcome in FL and suggest coexpression at the centrosome. Given the reported interaction of YY1 with PLK1 at the centriole and promotion of cell division at the G2/M checkpoint, the results would concord with the known association of higher proliferation with poor outcome in FL.

  • Lymphoma
  • Proliferation
  • Tumour Biology
  • Cancer
  • Cell Cycle Regulation

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