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The programme of the German Congress for Laboratory Medicine 2022 was essentially designed by the divisions of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL). Almost all chairpersons of the divisions organised a 90-min symposium on current topics, i.e. conceptualised the symposia and invited speakers. For this article all chairpersons summarised the lectures that were given within the symposia. The DGKL’s work is structured into 5 areas of expertise: Molecular Diagnostics, Learning & Teaching, Quality & Management, Laboratory & Diagnostics and Biobanks & Informatics. The areas of expertise are in turn subdivided into divisions. About the history of the establishment of this new structure within the DGKL you can find information in the editorial of this issue.

Programmed cell death, accidental cell degradation and active extrusion constantly lead to the release of DNA fragments into human body fluids from virtually all cell and tissue types. It is widely accepted that these cell-free DNA (cfDNA) molecules retain the cell-type specific genetic and epigenetic features. Particularly, cfDNA in plasma or serum has been utilized for molecular diagnostics. The current clinically implemented liquid biopsy approaches are mostly based on detecting genetic differences in cfDNA molecules from healthy and diseased cells. Their diagnostic potential is limited to pathologies involving genetic alterations, by the low proportion of cfDNA molecules carrying the mutation(s) relative to the total cfDNA pool, and by the detection limit of employed techniques. Recently, research efforts turned to epigenetic features of cfDNA molecules and found that the tissue-of-origin of individual cfDNA molecules can be inferred from epigenetic characteristics. Analysis of, e.g., methylation patterns, nucleosome or transcription factor binding site occupancies, fragment size distribution or fragment end motifs, and histone modifications determined the cell or tissue-of-origin of individual cfDNA molecules. With this tissue-of origin-analysis, it is possible to estimate the contributions of different tissues to the total cfDNA pool in body fluids and find tissues with increased cell death (pathologic condition), expanding the portfolio of liquid biopsies beyond genetics and towards a wide range of pathologies, such as autoimmune disorders, cardiovascular diseases, and inflammation, among many others. In this review, we give an overview on the status of tissue-of-origin approaches and focus on what is needed to exploit the full potential of liquid biopsies towards minimally invasive screening methods with broad clinical applications.

Genomes of diverse origins are continuously shed into human body fluids in the form of fragmented cell-free DNA (cfDNA). These molecules maintain the genetic and epigenetic codes of their originating source, and often carry additional layers of unique information in newly discovered physico-chemical features. Characterization of cfDNA thus presents the opportunity to non-invasively reconstruct major parts of the host- and metagenome in silico. Data from a single specimen can be leveraged to detect a broad range of disease-specific signatures and has already enabled the development of many pioneering diagnostic tests. Moreover, data from serial sampling may allow unparalleled mapping of the scantily explored landscape of temporal genomic changes as it relates to various changes in different physiological and pathological states of individuals. In this review, we explore how this vast dimension of biological information accessible through cfDNA analysis is being tapped towards the development of increasingly powerful molecular assays and how it is shaping emerging technologies. We also discuss how this departure from traditional paradigms of snapshot genetic testing may pave the way for an onrush of new and exciting discoveries in human biology.

Early detection is crucial for optimal treatment and prognosis of cancer. New approaches for pan-cancer screening comprise the comprehensive characterization of circulating tumor DNA (ctDNA) in plasma by next generation sequencing and molecular profiling of mutations and methylation patterns, as well as fragmentation analysis. These promise the accurate detection and localization of multiple cancers in early disease stages. However, studies with real screening populations have to show their clinical utility and practicability.

CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020–2021) and KEQAS (2020–2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%).Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from −29.28 to 9.86 %, into −0.09–0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from −23.78 to 2.00 % pre-harmonization to −3.13–1.42 % post-harmonization.The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs. [ABSTRACT FROM AUTHOR]

Legal regulations and guidelines such as the Guidelines of the German Medical Association for the Quality Assurance of Laboratory Medical Examinations (Rili-BAEK) and ISO 15189 apply to electronic laboratory reports. However, many laboratories struggle with practical implementation of these regulations and guidelines.

Point-of-care antigen tests (PoC-AgTs) for the rapid detection of SARS-CoV-2 infection enable screening of additional populations with less effort, independent of laboratories and at a low cost. PoC-AgTs have therefore been included in national testing strategies with additional quality requirements to address limitations in specificity and sensitivity. Information given in the package inserts of the test providers should enable the user to evaluate the performance of a PoC-AgT in advance. The quality of this information has been independently assessed since the Corona Test Ordinance came into force in Germany in October 2020.

Children with congenital heart disease (CHD) undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at risk for systemic inflammation leading to endothelial dysfunction associated with increased morbidity. Bioactive adrenomedullin (bio-ADM) is a peptide regulating vascular tone and endothelial permeability. The aim of this study was to evaluate the dynamics of plasma bio-ADM in this patient cohort and its role in capillary leak. Plasma samples from 73 pediatric CHD patients were collected for bio-ADM measurement at five different timepoints (TP) in the pre-, intra-, and post-operative period. The primary endpoint was a net increase in bio-ADM levels after surgery on CPB. Secondary endpoints included association of bio-ADM levels with clinical signs for endothelial dysfunction. Bio-ADM levels increased after surgery on CPB from pre-operative median of 12 pg/mL (IQR [interquartile range] 12.0–14.8 pg/mL) to a maximum post-operative median of 48.8 pg/mL (IQR 34.5–69.6 pg/mL, p<0.001). Bio-ADM concentrations correlated positively with post-operative volume balance, (r=0.341; p=0.005), increased demand for vasoactive medication (duration: r=0.415; p<0.001; quantity: TP3: r=0.415, p<0.001; TP4: r=0.414, p<0.001), and hydrocortisone treatment for vasoplegia (bio-ADM median [IQR]:129.1 [55.4–139.2] pg/mL vs. 37.9 [25.2–64.6] pg/mL; p=0.034). Patients who required pleural effusion drainage revealed higher bio-ADM levels compared to those who did not (median [IQR]: 66.4 [55.4–90.9] pg/mL vs. 40.2 [28.2–57.0] pg/mL; p<0.001). Bio-ADM is elevated in children after cardiac surgery and higher levels correlate with clinical signs of capillary leakage. The peptide should be considered as biomarker for endothelial dysfunction and as potential therapeutic target in this indication. [ABSTRACT FROM AUTHOR]

Laboratory information systems typically contain hundreds or even thousands of reference limits stratified by sex and age. Since under these conditions a manual plausibility check is hardly feasible, we have developed a simple algorithm that facilitates this check. An open-source R tool is available as a Shiny application at github.com/SandraKla/Zlog_AdRI. Based on the zlog standardization, we can possibly detect critical jumps at the transitions between age groups, regardless of the analytical method or the measuring unit. Its advantage compared to the standard z-value is that means and standard deviations are calculated from the reference limits rather than from the underlying data itself. The purpose of the tool is illustrated by the example of reference intervals of children and adolescents from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). The Shiny application identifies the zlog values, lists them in a colored table format and plots them additionally with the specified reference intervals. The algorithm detected several strong and rapid changes in reference intervals from the neonatal period to puberty. Remarkable jumps with absolute zlog values of more than five were seen for 29 out of 192 reference limits (15.1%). This might be attenuated by introducing shorter time periods or mathematical functions of reference limits over age. Age-partitioned reference intervals will remain the standard in laboratory routine for the foreseeable future, and as such, algorithmic approaches like our zlog approach in the presented Shiny application will remain valuable tools for testing their plausibility on a wide scale. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is the most frequent monogenic disorder (prevalence 1:250) in the general population. Early diagnosis during childhood enables pre-emptive treatment, thus reducing the risk of severe atherosclerotic manifestations later in life. Nonetheless, FH screening programs are scarce. VRONI offers all children aged 5–14 years in Bavaria a FH screening in the context of regular pediatric visits. LDL-cholesterol (LDL-C) is measured centrally, followed by genetic analysis for FH if exceeding the age-specific 95th percentile (130 mg/dl, 3.34 mmol/l). Children with FH pathogenic variants are treated by specialized pediatricians and offered a FH-focused training course by a qualified training center. Reverse cascade screening is recommended for all first-degree relatives. VRONI aims to prove the feasibility of a population-based FH screening in children and to lay the foundation for a nationwide screening program. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of the prostate health index (PHI) and of the percentage of [-2]proPSA (%[-2]proPSA) calculated with total and free PSA from non-Beckman Coulter manufacturers (Roche and Abbott), and compare it with the fully Beckman Coulter [-2]proPSA derivatives. In this study, 237 men (PSA: 2–10 μg/L) scheduled for prostate biopsy were enrolled. %[-2]proPSA and PHI were calculated with total and free PSA from three manufacturers. Beckman Coulter PSA and [-2]proPSA were performed on the Access 2 analyzer (Hybritech calibration). Roche PSA was performed on the cobas e411 and the Abbott PSA on the Architect i2000sr. Statistical analysis was performed, considering prostate cancer (PCa) as the outcome. Univariate analysis showed that all indices were predictors of cancer, irrespective of the manufacturer (p<0.001). The AUC was similar for all manufacturers, both for %[-2]proPSA (Beckman Coulter: 0.756; Roche: 0.770; Abbott: 0.756) and PHI (Beckman Coulter: 0.776; Roche: 0.785; Abbott: 0.778). When considering the cutoffs that allowed 90% sensitivity, [-2]proPSA derivatives calculated with Roche and Abbott PSA had similar specificities and predictive values when compared to Beckman Coulter. The percentage of missed cancers (8–9%) was the same between manufacturers. The percentage of spared biopsies was significantly higher with Roche's PHI (21.0%) and Abbott's PHI (20.6%) than with Beckman Coulter's PHI (17.2%). In the PSA range between 2 and 10 μg/L, [-2]proPSA derivatives maintain their diagnostic performance in PCa detection when calculated with PSA from Roche and Abbott. This can lead to a broader implementation of these indices in clinical laboratories worldwide. [ABSTRACT FROM AUTHOR]

Background: NT-proBNP is one of the most important biomarkers for the diagnosis and risk assessment of heart failure in adults. Age- and gender-independent reference intervals (RIs) have been reported. In contrast, RIs in children are strongly age-dependent, do not exist for all ages and reveal a right-skewed distribution. Accordingly, no common Z-score can be formed and a cross-age interpretive method, so far, is missing. Methods: Within the paper on hand, new evaluation techniques are applied to already published NT-proBNP study results and additionally to newly gained data. Upper limits (ULs), lower limits (LLs) and 50th percentiles are tested for power-like behavior as a function of age using linear regression analysis. Functions for continuous RIs are derived and reference limits are calculated on a per day basis. A corresponding Zlog formula is deduced and its usefulness is stated in two clinical examples. Results: The power-like behavior of NT-proBNP concentration from birth to 18 years is demonstrated. With age in days t and measured NT-proBNP value x in pg/mL, an age-specific Zlog value may directly be calculated using the equation: Zlog NT-proBNP = log x + 0.512 ⋅ log t − 3.417 1.489 + 0.014 ⋅ log t ⋅ 3.92 ${\rm{Zlo}}{{\rm{g}}_{{\rm{NT - proBNP}}}} = {{\log \;x + 0.512 \cdot \log \;t - 3.417} \over {1.489 + 0.014 \cdot \log \;t}} \cdot 3.92$ Conclusions: Using formulas for UL and LL, continuous RIs from 0 to 18 years may be obtained. Continuity corresponds to physiological changes in the body much better than discrete RIs. With the advent of an NT-proBNP-specific Zlog value, a cross-age Z-score equivalent is providing an easy interpretation aid in everyday pediatric practice. This new approach allows to identify clinical worsening much better, sooner and more clearly than previous absolute values. [ABSTRACT FROM AUTHOR]

The article offers information on measurement of tumors using luminescent oxygen channeling immunoassays (LOCI™)-based assays and electrochemiluminiscent immunoassays (ECLIA). Topics discussed include determination of prostate cancer using prostate-specific antigen (PSA) and free PSA (fPSA); use of chemiluminescence immunoassay in LOCI™ technology; and correlations between α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA).

Background: Soluble mesothelin-related peptide (sMRP) has shown great potential for malignant mesothelioma detection. However, data on comparison with other cancer and benign diseases as well as with other established lung cancer biomarkers are rare. Methods: In this study, SMRP was investigated in sera from 1506 individuals including 147 healthy donors, 285 patients with diverse benign diseases and 1074 patients with mesothelioma (n=39) and various malignant tumors (lung, gastrointestinal, gynecological, urological). For differential diagnosis of lung diseases, carcinoembryonic antigen, cytokeratin 19-fragments (CYFRA 21-1), neuron-specific enolase and squamous cell cancer antigen were determined additionally. Results: Ninety-fifth percentiles of sMRP serum levels in healthy persons were 1.2 nM, in patients with benign diseases between 2.0 and 3.8 nM and in cancer patients between 1.5 and 44.3 nM. Highest values were observed in mesothelioma (median 2.3 nM; 95th percentile 44.3 nM). When differential diagnostic capacity of cancer detection vs. the relevant benign control group was tested, sMRP showed best results for mesothelioma and ovarian cancer with a sensitivity of 45% and 37%, respectively, at 95% specificity. At 100% specificity vs. normal controls, sensitivity for mesothelioma detection was found to be 59% for sMRP, 73% for CYFRA 21-1 and 88% for the combination of both. At 95% specificity vs. all other lung diseases, sensitivity for mesothelioma was 48% for sMRP, 15% for CYFRA 21-1 and 46% for the combination of both. Conclusions: In summary, SMRP is a valuable serum biomarker that is specific at high concentrations for the detection of malignant mesothelioma. For screening purposes, the combination with CYFRA 21-1 improves the sensitivity at high specificity. [ABSTRACT FROM AUTHOR]

Hintergrund: S100 ist als nützlicher Biomarker für die Prognoseaschätzung und die Verlaufsbeobachtung bei Patienten mit malignem Melanom und in Patienten mit verschiedenen neurologischen Erkrankungen anerkannt. Das Ziel dieser Studie war, die Freisetzung und klinische Relevanz von S100 bei anderen benignen and malignen Erkrankungen jenseits dieser Indikationen zu untersuchen, um die Tumor- und Organspezifität von S100 zu bewerten. Methoden: S100-Konzentrationen wurden in Serumproben von 1856 unbehandelten Patienten ermittelt, darunter 59 gesunde Personen, 358 Patienten mit benignen Erkrankungen und 1439 Patienten mit malignen Tumoren. Ergebnisse: Gesunde Personen hatten niedrige S100 Serumwerte, die einen Median von 0.041 ng/mL, eine 95. Perzentile von 0.096 ng/mL und ein Maximum von 0.144 ng/mL erreichten. Die Mediane der Patientengruppen lagen bei benignen Erkrankungen zwischen 0.030 und 0.057 ng/mL, bei Patienten mit malignen Tumoren zwischen 0.020 und 0.059 ng/mL - und waren somit vergleichbar zu gesunden Kontrollpersonen. Lediglich 2% der Patienten mit benignen Erkrankungen, v.a. infektiösen, autoimmunen oder benignen gastrointestinalen Erkrankungen, sowie 1% der Patienten mit malignen Tumoren wiesen im Vergleich zu gesunden Personen leicht erhöhte Werte auf - in den meisten Fällen bis 0.5 ng/mL. Schlussfolgerung: Im Gegensatz zu vielen anderen onkologischen Biomarkern wird S100 nur selten in höheren Konzentrationen von den meisten benignen und malignen Erkrankungen - mit Ausnahme des malignen Melanoms und neurologischer Erkrankungen - freigesetzt, was sich in einer sehr hohen Organ- und Tumorspezifität widerspiegelt. Als möglicher Einflussfaktor sind schwere infektiöse Erkrankungen zu berücksichtigen. [ABSTRACT FROM AUTHOR]

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Background: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. Methods: The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD+8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycerides 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R=0.982, slope=0.921, intercept=+1.951). OV Monitor serum levels were low in healthy individuals (n=267, median=9.7 kU/L, 95th percentile=30.8 kU/L), higher in individuals with various benign diseases (n=549, medians=10.9–16.4 kU/L, 95th percentiles=44.2–355 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=12.4–445 kU/L; 95th percentiles=53.4–4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer [area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). Conclusions: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers. Clin Chem Lab Med 2008;46:588–99. [ABSTRACT FROM AUTHOR]

Background: Cancer antigen CA15-3 antigen is known as a valuable marker for the management of breast cancer. Methods: The analytical and clinical performance of the Access® BR Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA15-3 on the Elecsys® System (Roche Diagnostics). Results: Total imprecision (%CV) of the BR Monitor ranged between 5.5% and 11.7%, and inter-laboratory reproducibility between 3.4% and 5.1%. Linearity upon dilution showed a mean recovery of 98.5% (SD±9.1%). Endogenous interferents had no influence on BR Monitor levels (mean recoveries: hemoglobin 112%, bilirubin 111%, triglycerides 108%). There was no high-dose hook effect up to 13,540 kU/L. Clinical performance investigated in sera from 1811 individuals showed a general correlation between the Access BR Monitor and Elecsys CA15-3 (R=0.797), with a slope of 1.383. CA15-3 serum levels, as measured by the BR Monitor, were low in healthy individuals (n=267, median=11.9 kU/L, 95th percentile=23.5 kU/L), higher in individuals with various benign diseases (n=549, medians=11.3–15.6 kU/L, 95th percentiles=21.6–54.6 kU/L) and even higher in individuals suffering from various cancers (n=995, medians=11.2–22.8 kU/L, 95th percentiles=30.0–429.7 kU/L). Best diagnostic accuracy for cancer detection against the relevant benign control group by the BR Monitor was found for locoregional and metastatic breast cancer, as well as for ovarian cancer [area under the curve (AUC) 0.619, 0.897 and 0.774]. Results for the reference CA15-3 assay were comparable (AUC 0.611, 0.887 and 0.818). Conclusions: The Access BR Monitor provides accurate methodological characteristics and demonstrates an analytical and clinical correlation with Elecsys CA15-3. Best diagnostic accuracy for the BR Monitor was found in breast and ovarian cancer. Our results also suggest a clinical value of the BR Monitor in other cancers. Clin Chem Lab Med 2008;46:612–22. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access® GI Monitor assay (Beckman Coulter) was evaluated on the UniCel® DxI 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access® GI Monitor and Elecsys CA19-9 (R=0.959, slope=1.004, intercept=+0.17). GI Monitor serum levels were low in healthy individuals (n=267, median=6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n=550, medians=5.8–13.4 kU/L, 95th percentiles=30.1–195.5kU/L) and even higher in individuals suffering from various cancers (n=995, medians=8.4–233.8 kU/L, 95th percentiles=53.7–13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer [area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access® GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers. Clin Chem Lab Med 2008;46:600–11. [ABSTRACT FROM AUTHOR]

Between 1997 and 2000 we investigated in a prospective study the voided urine samples of all consecutive patients undergoing cystoscopy independent from their clinical background (n = 705) with the BTA-TRAK™ assay (Bard Diagnostics, Redmont, USA) detecting a complement factor H-related protein (CFHrP) and the NMP22 assay (Matritech, Newton, USA) measuring a nuclear matrix protein, which is supposed to be specific for bladder cancer. The individuals were divided into three groups concerning the clinical background: 233 patients had urological diseases, 268 patients had urinary bladder cancer and 150 patients had other urological malignancies. Based on the clinical findings we compared our results with well established diagnostic methods for urinary bladder cancer such as cytology and the detection of hematuria. In addition, we investigated urine samples from 30 healthy individuals and 24 patients with urinary tract infection without performing cystoscopy. Following the recommendations of the European Group on Tumor Markers we used 95% specificity for benign urological diseases and urinary tract infections, which resulted in a sensitivity of 17% for active bladder cancer for the BTA-TRAK™ assay and 31% for NMP22. We compared these results with the detection of hematuria (specificity: 72%) and cytology, which had a sensitivity of 64% and 89%, respectively. Subsequently, we calculated sensitivity and specificity for the detection of relapse of the disease. Again using 95% specificity, in this case for patients with recurrent disease the BTA-TRAK™ assay showed 8% sensitivity as compared to 12% for the NMP22 assay. Due to an insufficient specificity and sensitivity, both tests can neither be clinically useful in screening of high risk patients, nor in primary diagnosis of bladder cancer. They cannot replace neither cystoscopy nor cytology. In the follow-up care more investigations may be necessary to prove the benefit of existing diagnostic strategi... [ABSTRACT FROM AUTHOR]

This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra- and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (inter-laboratory median: 1.3%) and from 1.3 to 8.5 (inter-laboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and inter-assay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n = 723) and in patients with lung cancer (n = 333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n = 183), the cut-off value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n = 188) and was significantly higher (p < 0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n = 374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturer's declaration up to 370 ng/ml) and a short incubation time of 18 min. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including cell-free nucleic acid diagnostics, non-invasive prenatal testing, and analysis of cell-free Deoxyribonucleic acid (DNA).