Donal J Brennan1, Andreas Hackethal1, Alex M Metcalf2, Jermaine Coward3, Kaltin Ferguson2, Martin K Oehler4, Michael A Quinn5, Monika Janda6, Yee Leung7, Michael Freemantle8, Penelope M Webb2, Amanda B Spurdle2, Andreas Obermair9. 1. Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia. 2. Queensland Institute of Medical Research, Genetics and Computational Biology Division, 300 Herston Rd, Herston, Brisbane 4006, Australia. 3. Mater Medical Research Institute, South Brisbane, QLD, Australia. 4. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 5. Women's Cancer Research Centre, Royal Women's Hospital, Victoria, Australia. 6. School of Public Health, Queensland University of Technology, Brisbane, Australia. 7. School of Women's and Infants' Health, University of Western Australia, Perth, Australia. 8. Sullivan Nicolaides Pathology, Cnr Whitmore St & Seven Oaks St, Taringa, QLD 4068, Australia. 9. Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia. Electronic address: ao@surgicalperformance.com.
Abstract
OBJECTIVE: HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. METHODS: Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann-Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression analyses. RESULTS: Median CA125 and HE4 levels were higher in stage III and IV tumours (p<0.001) and in tumours with outer-half myometrial invasion (p<0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC)=0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC=0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR=2.40, 95% CI 1.19-4.83, p=0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR=2.86, 95% CI 1.25-6.51, p=0.012). CONCLUSION: These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy.
OBJECTIVE:HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. METHODS: Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann-Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression analyses. RESULTS: Median CA125 and HE4 levels were higher in stage III and IV tumours (p<0.001) and in tumours with outer-half myometrial invasion (p<0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC)=0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC=0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR=2.40, 95% CI 1.19-4.83, p=0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR=2.86, 95% CI 1.25-6.51, p=0.012). CONCLUSION: These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancerpatients who might benefit from lymphadenectomy.
Authors: Roberto Angioli; Stella Capriglione; Giuseppe Scaletta; Alessia Aloisi; Andrea Miranda; Carlo De Cicco Nardone; Corrado Terranova; Francesco Plotti Journal: Tumour Biol Date: 2015-11-03
Authors: A Stiekema; Car Lok; C M Korse; W J van Driel; V van der Noort; G G Kenter; K K Van de Vijver Journal: Virchows Arch Date: 2017-04-11 Impact factor: 4.064
Authors: Donal J Brennan; Andreas Hackethal; Kristy P Mann; Irene Mutz-Dehbalaie; Heidi Fiegl; Christian Marth; Andreas Obermair Journal: BMC Cancer Date: 2015-02-06 Impact factor: 4.430