J Gynecol Oncol.  2011 Dec;22(4):244-252. 10.3802/jgo.2011.22.4.244.

Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass

• Partheen K
• Kristjansdottir B
• Sundfeldt

• KMID: 2173626
• DOI: http://doi.org/10.3802/jgo.2011.22.4.244

Abstract

OBJECTIVE
Women presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer. We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care.
METHODS
Patients diagnosed with a cystic ovarian mass and scheduled for an operation at our center of excellence for ovarian cancer surgery from 2001 to 2010 were prospectively included (n=394) and plasma was collected consecutively. Cut-off for HE4 was calculated at 75% specificity (85 pM and 71.8 pM for post and premenopausal women). For CA-125, 35 U/mL cut-off was used. The study population included women with malignant (n=114), borderline (n=45), and benign (n=215) ovarian tumors.
RESULTS
Receiver operator characteristic (ROC) area under the curve (AUC) in the benign versus malignant cohorts was 86.8% for CA-125 and 84.4% for HE4. Negative predictive value was 91.7% when at least one of the biomarkers was positive, with only early stage epithelial ovarian cancer showing false negative results. Sensitivity at set specificity (75%) was 87% for risk of ovarian malignancy algorithm (ROMA) in the postmenopausal cohort (cut-off point, 26.0%) and 81% in the premenopausal cohort (cut-off point, 17.3%). ROC AUC in the benign versus stage I epithelial ovarian cancer was only 72% for HE4 and 76% for CA-125.
CONCLUSION
In our study, population HE4 did not outperform CA-125. Based on our data a prospective trial with patients already diagnosed with an ovarian cyst may be conducted.

Keyword

CA-125; Human epididymis protein 4; Ovarian cancer; Risk of ovarian malignancy algorithm

MeSH Terms

Area Under Curve
Biomarkers
Cohort Studies
Dietary Sucrose
Female
Humans
Neoplasms, Glandular and Epithelial
Ovarian Cysts
Ovarian Neoplasms
Plasma
Prospective Studies
Sensitivity and Specificity
Dietary Sucrose
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms

Figure

• 

  Fig. 1 Correlation between HE4 and CA-125. Logarithmic scales are used, and the dotted lines show cut-off values. HE4, 85 pM; CA-125, 35 U/mL.

• 

  Fig. 2 Receiver operating characteristic curves of benign vs. malignant cases. ROMA, risk of ovarian malignancy algorithm.

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