Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer.

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.

Median of patient results as a tool for assessment of analytical stability.

BACKGROUND: In spite of the well-established external quality assessment and proficiency testing surveys of analytical quality performance in laboratory medicine, a simple tool to monitor the long-term analytical stability as a supplement to the internal control procedures is often needed. METHOD: Patient data from daily internal control schemes was used for monthly appraisal of the analytical stability. This was accomplished by using the monthly medians of patient results to disclose deviations from analytical stability, and by comparing divergences with the quality specifications for allowable analytical bias based on biological variation. RESULTS: Seventy five percent of the twenty analytes achieved on two COBASs INTEGRA 800 instruments performed in accordance with the optimum and with the desirable specifications for bias. DISCUSSION: Patient results applied in analytical quality performance control procedures are the most reliable sources of material as they represent the genuine substance of the measurements and therefore circumvent the problems associated with non-commutable materials in external assessment. CONCLUSION: Patient medians in the monthly monitoring of analytical stability in laboratory medicine are an inexpensive, simple and reliable tool to monitor the steadiness of the analytical practice.