Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer

✍ Scribed by Yongjung Park; Yoonjung Kim; Eun Young Lee; Jong-Han Lee; Hyon-Suk Kim

• Book ID: 102273015
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 332 KB
• Volume: 130
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.26129

✦ Synopsis

Human epididymis protein 4 (HE4) is a new biomarker for the detection of ovarian cancer. We evaluated the analytical performance of a novel automated HE4 assay and established reference ranges of HE4 and CA125. We also compared the diagnostic performance of both biomarkers for ovarian cancer. Precision performances and linearity of the HE4 assay were assessed. Serum samples from 2,182 healthy and 72 pregnant women were also assayed for HE4 and CA125, and the 95%, 97.5% and 99% reference limits for both markers were calculated. Additionally, sera from 66 ovarian cancer and 257 benign gynecologic disease patients were tested to validate reference ranges and diagnostic performances. The total precision of the HE4 assay was <5% coefficient of variation for most of the levels evaluated. The linearity range of this assay was from 15.0 to 1100.0 pmol/L. The 97.5% upper reference limits for HE4 and CA125 were 33.2 pmol/L (95% confidence interval [CI], 32.2-34.0) and 38.3 U/mL (95% CI, 35.1-41.5), respectively. Using these values as cutoff points, the sensitivity and specificity of HE4 for differentiating ovarian cancer from benign gynecologic diseases and healthy individuals were 90.9% and 94.1%, and those of CA125 were 72.7% and 94.4%. The receiver operating characteristic-area under the curve values of HE4 and CA125 for discriminating ovarian cancer from age-matched control were 0.94 and 0.86, respectively, and they were statistically different (p 5 0.0095). The new automated HE4 assay showed good analytical and diagnostic performances. The reference limits established in our study could be used as cutoff levels to facilitate more accurate diagnosis of ovarian cancer in Asian population.

Ovarian cancer is a common malignant disease and is ranked fifth in causes of cancer-related mortalities in women. The American Cancer Society estimates that 21,880 new patients will suffer from ovarian cancer and 13,850 patients will die from it in the United States in 2010. Pelvic masses can be found in $20% of women in their lifetime, 2 and $15% to 20% of these cases will be diagnosed with ovarian cancer. 3 However, more than three-fourths of patients with ovarian cancer are diagnosed in the advanced stages, which is associated with a poor survival rate of about 10-20%, 4 although ovarian cancer has a good prognosis if detected in its early stages and when patient care by specialized clinicians and surgeons is provided. 5-7 Therefore, early detection and accurate differential diagnosis of ovarian cancer from benign pelvic masses is essential for improving patients' survival.

CA125 is the most commonly used tumor marker for detecting and monitoring ovarian cancer in current clinical practice. However, this glycoprotein is not expressed in up to 20% of ovarian cancer patients 8 and can be elevated in various benign or malignant conditions other than ovarian cancer. 9 Moreover, diagnostic performances of CA125 were not good enough for screening to detect early stage ovarian cancer in some studies. Therefore, many studies have been performed to improve the diagnostic performance of biomarkers or their combinations for ovarian cancer diagnosis. Some markers, including mesothelin, inhibin, kallikreins and osteopontin, have been investigated as possible improvements in the sensitivity and specificity for early and precise detection of ovarian cancer. Human epididymis protein 4 (HE4), also known as WAP four disulphide core 2 (WFDC2), is a novel protein and is one of the more promising biomarkers for improving diagnostic