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

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

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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.

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

Keywords

  • Journal Article
  • sarcoma
  • tumor biomarkers

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