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.

Long-term TCSs are at risk of premature hormonal aging. Our findings may pertain to cancer survivors in general, underlining the importance of extended follow-up.

Background: The primary aim of the study was to reduce interference in an in-house two-site, two-step immunometric assay. Methods: In the running laboratory routine, 11 261 samples were tested with a carcinoembryonic antigen (CEA) assay with bovine immunoglobulin but no murine immunoglobulins in the buffer, in parallel to our routine CEA assay, using 15 mg/L heat-treated nonspecific murine immunoglobulin (MAK33) in the buffer and with the Fc fragments removed from the capture antibody. Results: The frequency of interference was estimated to be 4.0% (95% confidence interval, 3.3–4.7%). The addition of 15 mg/L native MAK33 had little effect (frequency, 3.9%; 95% confidence interval, 3.2–4.6%), whereas adding 15 mg/L heat-treated MAK33 reduced interference to 0.86% (0.61–1.12%), and adding 50 mg/L reduced it further to 0.06% (0–0.13%). Removing the Fc fragments by itself reduced interference to 0.10% (0.02–0.19%). There were no statistically significant differences for age (P <0.23) or gender (P <0.40) between patients with interference (n = 210) and a randomly selected interference-negative control group (n = 186). Interference was not constant in patients: 15 of 25 individuals positive for interference and with four or more samples screened for interference had an interference-negative sample either before or after the peak of interference. Conclusions: In a two-site, two-step immunometric assay using mouse monoclonal antibodies, use of heat-treated nonspecific murine immunoglobulin in the buffer or removal of the Fc fragment from the capture antibody could improve performance.

The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important.

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