ABSTRACT
BACKGROUND/AIMS: The determination of neuron-specific enolase (NSE) is relatively frequently requested in the differential diagnosis of small-cell lung carcinoma and non-small-cell lung carcinoma. The individual results of different immunoassays are often not comparable, which has been confirmed by long-term external quality assessments. In this study, we assessed the possible sources of these differences. METHODS: More than 3,000 NSE analyses were performed using seven different immunoassays: DELFIA (PerkinElmer), Elecsys 2010 or Modular Analytics E 170 (Roche), Kryptor (B.R.A.H.M.S.), the enzyme-linked immunosorbent assay DRG and three assays based on immunoradiometric assays (DiaSorin, Immunotech and Schering-CIS). The following parameters were evaluated: precision profile of the individual methods, linearity on dilution and modified recovery, comparability and discrimination of immunoassays, sensitivity, and specificity. RESULTS: There were differences in the correlation of values of certain low-concentration specimens. Some assays correlate well while others do not (up to fivefold difference), especially in the case of controls prepared synthetically. Therefore, the current non-standardized preparation of controls is questionable in our opinion. In the cutoff range, the difference in the results of native samples did not exceed its double value. The variation in values >100 microg/l obtained with different assays is <40%. CONCLUSION: Our results confirmed expected matrix interferences especially in the range of normal and cutoff NSE concentrations. Another source of discrepancies can be attributed to different antibody affinity to alphagamma- and gammagamma-enolase isoenzymes. Finally, improper settings of cutoff values also contribute to the different discrimination of the methods.
Subject(s)
Biological Assay , Biomarkers, Tumor/metabolism , Lung Neoplasms/enzymology , Phosphopyruvate Hydratase/blood , Adenocarcinoma/blood , Adenocarcinoma/enzymology , Carcinoma, Large Cell/blood , Carcinoma, Large Cell/enzymology , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Small Cell/blood , Carcinoma, Small Cell/enzymology , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/enzymology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Humans , Lung Neoplasms/blood , Sensitivity and SpecificityABSTRACT
In this study we performed the CHEK2 c.1100delC mutation analysis in 1046 breast cancer patients and 730 unaffected control individuals. The mutated allele was found in 3 out of 688 unselected sporadic breast cancer patients and in 1 out of 358 familial/early onset breast cancer patients. Two mutations were identified in a cohort of 730 controls. Our results support the finding that frequency of CHEK2 c.1100delC mutation varies among different populations. Based on our results, genotyping of CHEK2 c.1100delC mutation in clinical settings in the Czech Republic could not be recommended.
Subject(s)
Breast Neoplasms, Male/epidemiology , Breast Neoplasms, Male/genetics , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Germ-Line Mutation , Protein Serine-Threonine Kinases/genetics , Adult , Case-Control Studies , Checkpoint Kinase 2 , Czech Republic/epidemiology , DNA Mutational Analysis , Female , Humans , Male , Middle Aged , RiskABSTRACT
MUC1 mucins are tumour markers that are frequently indicated and examined, particularly as part of the treatment of breast cancer. Relatively large differences were observed in external quality assessment (EQA) between the results that were obtained by different immunoassay technologies. Thus, we compared eight routinely employed immunoassay sets for the determination of MUC1 mucins in the serum: six closed automated systems (AxSYM, Centaur, ECi Vitros, Elecsys 2010, Immulite 2000 and Kryptor), and two IRMA kits (ELSA CIS and IRMA-mat Byk-Sangtec). Using all analytical systems, we measured identical groups of clinical samples complete with selected calibrator and control samples. The repeatability of measurements (presented as coefficients of variation) ranged from 0.7% (Kryptor) to 6.9% (Immulite 2000). Even though the cut-off values differ among various systems, no similar clinical efficacy appears to be attained. In the region of cut-off values, the highest specificity that was set as a standard was found for the AxSYM analyser, while the sensitivity was highest for the Elecsys 2010. Data from Bland-Altman differential plots suggest the presence of significant individual differences among individual samples, mainly in the region of high concentrations of MUC1 mucins. The parameters of Passing-Bablok regression show significant systematic differences between some of the analytical systems as well as an increase of the differences with increasing MUC1 mucin concentrations. The effect of the combination of antibodies used on the extent of differences among results obtained with individual systems is more obvious than the effect of the matrix of analysed materials.
