Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers

Objectives: Tumor markers are well-known for being important tools in the support of diagnosis, monitoring of treatment efficacy and follow-up of cancers. CA 125, CA 15-3 and HE 4 have demonstrated potential efficacy in other clinical indications. The main objective was to evaluate the biological variation of these glycoproteins using two different immunoassays in an apparently healthy Caucasian population.

Methods: Nineteen healthy volunteers including 11 women and 8 men were sampled weekly for 5 consecutive weeks. Samples were analyzed in duplicate on Lumipulse^® G600II (Fujirebio) and on the Cobas e602 (Roche Diagnostics) analyzers. After assessment of normality, exclusion of outliers and analysis of homogeneity of variance, analytical variation (CV_A), within-subject biological variation (CV_I) and between-subject biological variation (CV_G) were determined using a nested ANOVA.

Results: CV_A, CV_I and CV_G were determined on both analyzers and both genders. For CA 125, the CV_A ranges from 1.0 to 3.4%, the CV_I from 5.7 to 13.8% and the CV_G from 32.2 to 42.9%. For CA 15-3, the CV_A is between 1.1 and 3.4%, the CV_I between 3.9 and 6.5% and the CV_G between 43.7 and 196.9%. Lastly, HE 4 has CV_A values between 1.4 and 2.4%, CV_I between 5.1 and 10.5% and CV_G between 7.1 and 12.6%.

Conclusions: Our study provided updated data on the biological variation of CA 125, HE 4 and CA 15-3. These data allow to improve the clinical interpretation and thus the management of the patient.