Automated scoring can be used to assess hypoxia marker expression in soft tissue sarcoma


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Robert Potter1,Laura Forker2,Stefano Sioletic3,Patrick Shenjere4,Darren Roberts2,Joely Irlam2,Helen Valentine2,Ana Hughes5,Piers Gaunt5,Lucinda Billingham5,David Hughes6,Martin Robinson7,Catharine West2
1University of Manchester,2Translational Radiobiology Group, Institute of Cancer Sciences, University of Manchester,3Department of Pathology, General University Hospital, Udine, Italy,4The Christie NHS Foundation Trust, Manchester,5Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham,6Sheffield Teaching Hospitals, Sheffield Teaching Hospitals NHS Trust,7Academic Unit of Clinical Oncology, Weston Park Hospital

Abstract

Background

Hypoxia is associated with risk of distant metastasis in localised, high grade soft tissue sarcoma (STS).  A reliable hypoxia biomarker may identify patients for intensification of therapy or hypoxia targeting. The markers CAIX and HIF-1α have been associated with poor disease free survival in STS in the phase III UK VorteX trial cohort. Manual immunohistochemistry (IHC) scoring is time consuming and requires specialist pathology advice. This study aimed to investigate whether automated software could be used to assess hypoxia marker expression.

Method

Tissue microarrays were constructed from 301 patients registered in the VorteX trial (3 cores/patient) and stained via singleplex IHC for CAIX, GLUT-1 and HIF-1α. The percentage of tumour cells stained and staining intensity was estimated twice by one scorer and independently by a sarcoma pathologist, and a consensus score obtained. Automated scoring was performed using Definiens Tissue Studio (Definiens, Munich, Germany). Manual and automated scores were compared via Pearson product-moment correlation.

Results

849 cores encompassing multiple STS subtypes were analysed. There was a high correlation between manual and automated scoring across all hypoxia markers for both H-scores (CAIX r=0.816, GLUT-1 r=0.829, HIF-1α r=0.788) and percentage positivity (CAIX r=0.821, GLUT-1 r=0.792, HIF-1α r=0.804).

Conclusion

Automated scoring using Definiens Tissue Studio is a valid alternate to manual review for scoring hypoxia markers in STS. Automation will reduce analysis time and the need for specialist pathology input, and may therefore be a useful method for possible future hypoxia biomarker driven trials in STS.

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