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

Abstract

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.

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

“…Our results are somewhat consistent with those of previous studies (Hellström et al, 2003;Moore et al, 2008;Huhtinen et al, 2009;Montagnana et al, 2009;Moore et al, 2009;Moore et al, 2010;Nolen et al, 2010;Bandiera et al, 2011;Molina et al, 2011;Park et al, 2011;Van Gorp et al, 2011;Karlsen et al, 2012;Park et al, 2012), which reported that serum CA125 and HE4 levels were significantly higher in ovarian cancer women than those in benign ovarian tumor women and in healthy women. In accordance with previous observations , our results showed that serum CA125 and HE4 levels were found to be related to FIGO stage with higher concentrations in late stages (stage III/IV) than in early stages (stage I/II).…”

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

“…In contrary to the above reports, a study on 2400 healthy employees of a Korean hospital indicated that the reference limits of HE4 tended to elevate with age slightly, and no significant difference was found among 30-60-year-old individuals [42]. The age span covered in this study is relatively narrow, and it is unclear if this discrepancy might be caused by the race factor.…”

Human Epididymis Protein 4 Reference Intervals in a Multiethnic Asian Women Population

“…HE4 has been developed and proposed as a potential serum marker for detection . Many studies have been conducted on its clinical utility and reference ranges (Bolstad and Oijordsbakken, 2012;Moore et al, 2012;Park et al, 2012). Most of them were carried out on Caucasian women with few studies involving Asian women.…”

“…All three major ethnicity were involved. Park et al (2012) had established the reference limit for HE4 and CA125 in a 2,400 healthy South Korean women (Park et al, 2012). They showed that the reference limit of HE4 increases with age (50-65 year) but those of CA125 tend to decreased.…”

“…In our study, the upper reference limit is two times higher in all group (pre and postmenopausal) as compared with the South Korean study (Park et al, 2012), (64.6 vs 33.2 pmol/L). However, our data seems to concur with data from the Norway (Bolstad and Oijordsbakken, 2012), but lower than the values found by Moore (2012).…”