Imagestream detection and characterisation of circulating tumour cells - a liquid biopsy for Hepatocellular Carcinoma?

  1. Lookup NU author(s)
  2. Laura Ogle
  3. Dr James Orr
  4. Catherine Willoughby
  5. Dr Claire Hutton
  6. Dr Stuart McPherson
  7. Professor Ruth Plummer
  8. Dr David Jamieson
  9. Professor Helen Reeves
Author(s)Ogle LF, Orr JG, Willoughby CE, Hutton C, McPherson S, Plummer R, Boddy AV, Curtin NC, Jamieson D, Reeves HL
Publication type Article
JournalJournal of Hepatology
ISSN (print)0168-8278
ISSN (electronic)1600-0641
Full text is available for this publication:
Background The lack of progress in developing and delivering new therapies for hepatocellular carcinoma (HCC) is in part attributed to the risk related avoidance of tumour biopsy at diagnosis. Circulating tumour cells (CTCs) are a potential source of tumour tissue that could aid biological or biomarker research, treatment stratification and monitoring. Methods An imaging flow cytometry method, using immunofluorescence of cytokeratin, EpCAM, AFP, glypican-3 and DNA-PK together with analysis of size, morphology and DNA content, for detection of HCC CTCs was developed and applied to 69 patient and 31 control samples. The presence of CTCs as a prognostic indicator was assessed in multivariate analyses encompassing recognised prognostic parameters.Results Between 1 and 1642 CTCs were detected in blood samples from 45/69 HCC patients compared to 0/31 controls. CTCs positive for the epithelial markers cytokeratin and EpCAM were detected in 29% and 18% of patients respectively, while an additional 28% of patients had CTCs negative for all markers other than size and evidence of hyperploidy. CTC number correlated significantly with tumour size and portal vein thrombosis (PVT). The median survival of patients with >1 CTC was 7.5 months versus >34 months for patients with <1 CTC (p <0.001, Log rank), with significance retained in a multivariate analysis (HR 2.34, 95% CI 1.005-5.425, p=0.049) including tumour size and PVT.Conclusions The use of multiple parameters enhanced HCC CTC detection sensitivity, revealing biological associations and predictive biomarker potential that may be able to guide stratified medicine decisions and future research.
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