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

doi:10.1038/bjc.2017.430

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

Cancer Clinical Trials Unit

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	698-704
Journal	British Journal of Cancer
Volume	118
Issue number	5
Early online date	12 Dec 2017
DOIs	https://doi.org/10.1038/bjc.2017.430
Publication status	Published - 6 Mar 2018

Keywords

Journal Article
sarcoma
tumor biomarkers

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Cite this

Forker, L., Gaunt, P., Sioletic, S., Shenjere, P., Potter, R., Roberts, D., Irlam, J., Valentine, H., Hughes, A., Billingham, L., Grimer, R., Seddon, B., Choudhury, A., Robinson, M., West, C. M. L., & David, H. (2018). The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma. British Journal of Cancer, 118(5), 698-704. Advance online publication. https://doi.org/10.1038/bjc.2017.430

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

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.",

keywords = "Journal Article, sarcoma , tumor biomarkers",

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

year = "2018",

month = mar,

day = "6",

doi = "10.1038/bjc.2017.430",

language = "English",

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pages = "698--704",

journal = "British Journal of Cancer",

issn = "0007-0920",

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Forker, L, Gaunt, P, Sioletic, S, Shenjere, P, Potter, R, Roberts, D, Irlam, J, Valentine, H, Hughes, A, Billingham, L, Grimer, R, Seddon, B, Choudhury, A, Robinson, M, West, CML & David, H 2018, 'The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma', British Journal of Cancer, vol. 118, no. 5, pp. 698-704. https://doi.org/10.1038/bjc.2017.430

TY - JOUR

T1 - The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort:

T2 - an important resource for translational research in soft tissue sarcoma

AU - Forker, Laura

AU - Gaunt, Piers

AU - Sioletic, Stefano

AU - Shenjere, Patrick

AU - Potter, Robert

AU - Roberts, Darren

AU - Irlam, Joely

AU - Valentine, Helen

AU - Hughes, Ana

AU - Billingham, Lucinda

AU - Grimer, Rob

AU - Seddon, Beatrice

AU - Choudhury, Ananya

AU - Robinson, Martin

AU - West, Catharine M L

AU - David, Hughes

PY - 2018/3/6

Y1 - 2018/3/6

N2 - 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.

AB - 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.

KW - Journal Article

KW - sarcoma

KW - tumor biomarkers

U2 - 10.1038/bjc.2017.430

DO - 10.1038/bjc.2017.430

M3 - Article

C2 - 29235571

SN - 0007-0920

VL - 118

SP - 698

EP - 704

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 5

ER -