The importance of individual biology in the clinical use of serum biomarkers for ovarian cancer.

BACKGROUND An increased focus on the biological behaviour of serum biomarkers for ovarian cancer, i.e., carbohydrate antigen 125 (CA-125) and human epididymis protein 4 (HE4), has been advocated to improve their clinical use. Due to the paucity and poor design of available studies evaluating biological variation (BV) of CA-125 and the lack of BV data for HE4, in this study we evaluated BV of both biomarkers. METHODS Monthly we obtained serum samples from 14 pre- (PreM) and 14 post-menopausal (PostM) healthy women for 4 consecutive months. Once all samples were available, they were analysed in a single run in duplicate for CA-125 and HE4 on Roche Modular system. Data were analysed by ANOVA. RESULTS For both biomarkers no difference in median concentrations was found between PreM and PostM. For CA-125 the intra-individual CV (CVI) was not different between groups (9.1% in both). For HE4 CVI was higher in PreM (12.1%) than in PostM (6.5%) (p<0.001). Between-subject CVs were 10.6% for CA-125 and 16.4% for HE4, with no influence by the fertility status. Both biomarkers showed high individuality meaning that the use of population-based reference limits may have limited value for their interpretation. Reference change values were 26% for CA-125 (all), 34% for HE4 PreM and 18% for HE4 PostM. CONCLUSIONS Monitoring longitudinal changes in serum concentrations of ovarian cancer biomarkers over time is probably better than using single threshold rules. According to differences in BV due to the hormonal status, one should differently interpret HE4 changes in PreM and PostM.