The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

Research output: Contribution to journalArticle

Authors

  • Laura Forker
  • Stefano Sioletic
  • Patrick Shenjere
  • Robert Potter
  • Darren Roberts
  • Joely Irlam
  • Helen Valentine
  • David Hughes
  • Ana Hughes
  • Rob Grimer
  • Beatrice Seddon
  • Ananya Choudhury
  • Martin Robinson
  • Catharine M L West

Colleges, School and Institutes

External organisations

  • Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
  • Department of Pathology, Ospedale S.Camillo de Lellis, Rieti 02100, Italy.
  • Department of Histopathology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
  • Department of Histopathology, Sheffield Teaching Hospitals NHS Trust, Weston Park Hospital, Whitham Road, Sheffield S10 2SJ, UK.
  • Department of Orthopaedic Oncology, Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Northfield, Birmingham B31 2AP, UK.
  • Department of Oncology, University College London Hospitals NHS Foundation Trust, 1st Floor Central, 250 Euston Road, London NW1 2PG, UK.
  • Department of Oncology, Academic Unit of Clinical Oncology (Cancer Clinical Trials Centre), Weston Park Hospital, Whitham Road, Sheffield S10 2SJ, UK.

Abstract

BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial.

METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression.

RESULTS: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis.

CONCLUSIONS: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity.British Journal of Cancer advance online publication, 12 December 2017; doi:10.1038/bjc.2017.430 www.bjcancer.com.

Details

Original languageEnglish
Pages (from-to)698-704
JournalBritish Journal of Cancer
Volume118
Issue number5
Early online date12 Dec 2017
Publication statusPublished - 6 Mar 2018

Keywords

  • Journal Article, sarcoma , tumor biomarkers