Assessment of biological variation and analytical imprecision of CA 125, CEA, and TPA in relation to monitoring of ovarian cancer

OBJECTIVES: Changes in serial tumor marker results during monitoring of patients with ovarian cancer are due not only to deterioration or amelioration of the patient's condition, but also to preanalytical sources of variation (CPP), total random analytical error, and within-subject normal biological variation. The aim of the study was to assess (i) the analytical imprecision (CVA) and the average inherent intra- and interindividual biological variation (CVTI and CVG, respectively) for CA 125, CEA, and TPA in a group of healthy women; (ii) the significance of changes in serial results of each marker; and (iii) the index of individuality.

METHODS: The study group consisted of 31 healthy women. Sixteen blood samples from each subject were collected in four series over a period of approximately 1 year. Data analysis was based on ANOVA. The index of individuality was calculated as ((CV2A + CV2TI)/CV2G)1/2 and the critical difference for a change between two consecutive concentrations as radical2xZx(CV2P + CV2A + CV2TI)1/2 (Z = 1.65 for unidirectional and 1.96 for bidirectional changes, P </= 0.05).

RESULTS: The averages of CVTI and CVG were 35.5 and 70.6% for CA 125, 13.9 and 58.3% for CEA, and 31.4 and 62.5% for TPA, respectively. The indices of individuality were 0.5 for CA 125, 0.3 for CEA, and 0.5 for TPA. The critical differences of CA 125, CEA, and TPA were 84.6, 37.6, and 76. 3%, respectively (Z = 1.65). There were no significant differences in CA 125, CEA, and TPA concentrations between smokers and nonsmokers or in CA 125 and CEA concentrations between pre- and postmenopausal women. Postmenopausal women had higher TPA concentrations than premenopausal (P = 0.015).

CONCLUSION: CVA and CVTI contribute considerably to the variation in serial results and should, therefore, be included in the criteria for serum tumor marker assessment during monitoring of patients with ovarian cancer.