Serum HE4 as a prognostic marker in endometrial cancer - A population based study

D.J. Brennan, A Hackethal, A.M. Metcalf, J Coward, K Ferguson, M.K. Oehler, M.A. Quinn, M Janda, Yee Leung, M Freemantle, P.M. Webb, A.B. Spurdle, A Obermair

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    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.
    Original languageEnglish
    Pages (from-to)159-165
    JournalGynecologic Oncology
    Volume132
    Issue number1
    Early online date6 Nov 2013
    DOIs
    Publication statusPublished - Jan 2014

    Fingerprint

    Endometrial Neoplasms
    Area Under Curve
    Biomarkers
    Serum
    Population
    Multivariate Analysis
    Neoplasms
    Survival Analysis
    Nonparametric Statistics
    Lymph Node Excision
    Regression Analysis
    Phenotype
    Recurrence
    Survival

    Cite this

    Brennan, D. J., Hackethal, A., Metcalf, A. M., Coward, J., Ferguson, K., Oehler, M. K., ... Obermair, A. (2014). Serum HE4 as a prognostic marker in endometrial cancer - A population based study. Gynecologic Oncology, 132(1), 159-165. https://doi.org/10.1016/j.ygyno.2013.10.036
    Brennan, D.J. ; Hackethal, A ; Metcalf, A.M. ; Coward, J ; Ferguson, K ; Oehler, M.K. ; Quinn, M.A. ; Janda, M ; Leung, Yee ; Freemantle, M ; Webb, P.M. ; Spurdle, A.B. ; Obermair, A. / Serum HE4 as a prognostic marker in endometrial cancer - A population based study. In: Gynecologic Oncology. 2014 ; Vol. 132, No. 1. pp. 159-165.
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    title = "Serum HE4 as a prognostic marker in endometrial cancer - A population based study",
    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.",
    author = "D.J. Brennan and A Hackethal and A.M. Metcalf and J Coward and K Ferguson and M.K. Oehler and M.A. Quinn and M Janda and Yee Leung and M Freemantle and P.M. Webb and A.B. Spurdle and A Obermair",
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    Brennan, DJ, Hackethal, A, Metcalf, AM, Coward, J, Ferguson, K, Oehler, MK, Quinn, MA, Janda, M, Leung, Y, Freemantle, M, Webb, PM, Spurdle, AB & Obermair, A 2014, 'Serum HE4 as a prognostic marker in endometrial cancer - A population based study' Gynecologic Oncology, vol. 132, no. 1, pp. 159-165. https://doi.org/10.1016/j.ygyno.2013.10.036

    Serum HE4 as a prognostic marker in endometrial cancer - A population based study. / Brennan, D.J.; Hackethal, A; Metcalf, A.M.; Coward, J; Ferguson, K; Oehler, M.K.; Quinn, M.A.; Janda, M; Leung, Yee; Freemantle, M; Webb, P.M.; Spurdle, A.B.; Obermair, A.

    In: Gynecologic Oncology, Vol. 132, No. 1, 01.2014, p. 159-165.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Serum HE4 as a prognostic marker in endometrial cancer - A population based study

    AU - Brennan, D.J.

    AU - Hackethal, A

    AU - Metcalf, A.M.

    AU - Coward, J

    AU - Ferguson, K

    AU - Oehler, M.K.

    AU - Quinn, M.A.

    AU - Janda, M

    AU - Leung, Yee

    AU - Freemantle, M

    AU - Webb, P.M.

    AU - Spurdle, A.B.

    AU - Obermair, A

    PY - 2014/1

    Y1 - 2014/1

    N2 - 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.

    AB - 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.

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    Brennan DJ, Hackethal A, Metcalf AM, Coward J, Ferguson K, Oehler MK et al. Serum HE4 as a prognostic marker in endometrial cancer - A population based study. Gynecologic Oncology. 2014 Jan;132(1):159-165. https://doi.org/10.1016/j.ygyno.2013.10.036