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

Background Despite high metastasis rates, adjuvant/neo-adjuvant 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 (FFPE) 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 203/216 randomised patients. High CAIX expression was associated with worse DFS (HR 2.28, 95%CI 1.44-3.59, p<0.001). HIF-1α and GLUT1 were not prognostic. CAIX remained prognostic in multivariable analysis. Conclusion 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 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.