Human epididymis protein 4 reference limits and natural variation in a Nordic reference population

Abstract

The objectives of this study are to establish reference limits for human epididymis protein 4, HE4, and investigate factors influencing HE4 levels in healthy subjects. HE4 was measured in 1,591 samples from the Nordic Reference Interval Project Bio-bank and Database biobank, using the manual HE4 EIA (Fujirebio) for 802 samples and the Architect HE4 (Abbott) for 792 samples. Reference limits were calculated using the statistical software R. The influence of donor characteristics such as age, sex, body mass index, smoking habits, and creatinine on HE4 levels was investigated using a multivariate model. The study showed that age is the main determinant of HE4 in healthy subjects, corresponding to 2% higher HE4 levels at 30 years (compared to 20 years), 9% at 40 years, 20% at 50 years, 37% at 60 years, 63% at 70 years, and 101% at 80 years. HE4 levels are 29% higher in smokers than in nonsmokers. In conclusion, HE4 levels in healthy subjects are associated with age and smoking status. Age-dependent reference limits are suggested.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-011-0256-4) contains supplementary material, which is available to authorized users.

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

“…We also noted that reference limits (95% reference interval with 90%CI) for HE4 in our study increases with menopausal state (58.4 pmol/L and 69.0 pmol/L for the pre and post menopausal groups respectively), but this could merely reflecting the increasing in age rather than being menopausal status per se. Similar trend were noted in studies on Caucasian women showing inclination of HE4 concentration to increase with age (Bolstad and Oijordsbakken, 2012;Moore et al, 2012). Our study also showed a significant difference in HE4 concentrations between the ethnicities (Malays and Indians).…”

“…However, our data seems to concur with data from the Norway (Bolstad and Oijordsbakken, 2012), but lower than the values found by Moore (2012). We also noted that our proposed reference limit are lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group).…”

“…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.…”

“…High BMI was noted to be associated with lower HE4 values while higher creatinine levels are associated with high HE4 values. The proposed reference limits are agedependent, ranging from 49.1-52.6 pmol/L (18-50 years old) and 54.1-72.6 pmol/L (55-86 years old) (Bolstad and Oijordsbakken, 2012) . The difference in concentration of HE4 between sexes is relatively small.…”

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

“…Gender and age are considered the main denominators of HE4 levels [35,41]. Generally, HE4 levels in healthy women are higher than those in healthy men (median 26.2 pM vs. 40.4 pM) presumably due to the HE4 expression in woman's reproductive organs.…”