POPULARITY
Background: Pro-gastrin releasing peptide ( ProGRP) concentrations in blood play an important role in the diagnosis and treatment of patients with small cell lung cancer (SCLC). The automated quantitative ARCHITECT (R) ProGRP assay was developed to aid in the differential diagnosis and in the management of SCLC. The purpose of this study was to evaluate the analytical performance of this chemiluminescent microparticle immunoassay at multiple sites. Methods: ARCHITECT ProGRP measures ProGRP using a two-step sandwich using monoclonal anti-ProGRP antibodies coated on paramagnetic microparticles and labeled with acridinium. Analytical performance of the assay was evaluated at four sites: Abbott Japan, Denka Seiken, the Johns Hopkins University, and the University of Munich. Results: Total precision (%CV) for nine analyte concentrations was between 2.2 and 5.7. The analytical sensitivity of the assay was between 0.20 pg/mL and 0.88 pg/mL. The functional sensitivity at 20% CV was between 0.66 pg/mL and 1.73 pg/mL. The assay was linear up to 50,000 pg/mL using a 1:10 autodilution protocol. The calibration curve was stable for 30 days. Comparison with the Fujirebio microtiter plate enzyme-linked immunosorbent assay (EIA) ProGRP assay gave a slope of 0.93 and a correlation coefficient (r) of 0.99. Conclusions: These results demonstrate that the ARCHITECT ProGRP assay has excellent sensitivity, precision, and correlation to a reference method. This assay provides a convenient automated method for ProGRP measurement in serum and plasma in hospitals and clinical laboratories. Clin Chem Lab Med 2009;47:1557-63.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 09/19
Es handelt sich um eine bizentrische, retrospektive Studie am Institut für Klinische Chemie am Klinikum Großhadern, München und an der Asklepioslungenfachklinik Gauting. Anhand von insgesamt 2749 Patienten wurde univariat und multivariat analysiert, inwieweit die Tumormarker CEA, CYFRA 21-1, NSE und ProGRP und zusätzlich die Routinelaborparameter eine Hilfestellung sowohl in der Diagnostik und Differentialdiagnostik eines Lungenrundherdes (benigne Lungenerkrankung, primäres Lungenkarzinom, Lungenmetastasen), als auch bei der Stadiumeinteilung und der histologischen Differenzierung (NSCLC mit Untergruppen oder SCLC) eines Lungenkarzinoms geben können. Alle vier Tumormarker differenzieren signifikant zwischen malignen und benignen Lungenerkrankungen, wobei CYFRA 21-1 das beste Sensitivität/Spezifitätverhältnis zeigte (AUC=0,777 in Großhadern, AUC=0,830 in Gauting), während CEA und ProGRP mit 8-13% Sensitivität die besten Marker bei 100% iger Spezifität waren. Zusätzlich konnten andere Laborparameter (Leukozyten, Erythrozyten, Hämoglobin, Thrombozyten, LDH, Glucose, CRP)signifikant zwischen benignem und malignem Lungenrundherd unterscheiden. Die Wertlagen von CEA, CYFRA 21-1 und NSE stiegen signifikant mit dem Tumorstadium an. Für die Differenzierung in NSCLC und SCLC waren NSE (AUC=0,802 in Großhadern, AUC=0,829 in Gauting)und ProGRP (AUC=0,759 in Großhadern, AUC=0,851 in Gauting)am hilfreichsten. Der Median für CEA lag in der Gruppe mit Adenokarzinomen am höchsten (Median: Großhadern 4,6 ng/ml, Gauting 7,9 ng/ml), für CYFRA 21-1 in der Gruppe mit Plattenepithelkarzinomen (Median: Großhadern 3,0 ng/ml, Gauting 5,3 ng/ml). Durch den multivariaten Einsatz der Tumormarker und eventuell zusätzlicher Routinelaborparameter wird eine additive Aussagekraft sowohl für die Differenzierung zwischen malignen und benignen Lungenerkrankungen als auch für die histologische Differenzierung in NSCLC und SCLC erlangt.
We retrospectively studied the single and combined diagnostic value of carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP), which were routinely analysed in patients with lung tumours of unknown origin at the time of admission to hospital. Inclusion criteria were the determination of CEA (AxSYM/Abbott), CYFRA 21-1 (ElecSys/Roche) and NSE (Kryptor/Brahms). We examined 1747 patients, where 1325 suffered from lung cancer (LC; small cell lung cancer, SCLC: n=194; non-small cell lung cancer, NSCLC: n = 1015; others: n = 116), 318 from benign lung diseases and 104 from lung metastases due to another primary malignancy. As ProGRP (ELISA ALSI/IBL) became available only recently, there are less data points of this marker. In total, 99.8% of LC patients released at least one of the four biomarkers (defined as values exceeding the median of healthy controls), and for the discrimination between benign disease (BID) and malignant lung disease each marker reached 100% tumour specificity at high levels (CEA: 20 ng/mL; CYFRA 21-1: 40 ng/mL; NSE: 45 ng/mL; ProGRP: 250 pg/mL). At a specificity of > 99%, ProGRP reached the highest diagnostic efficacy for SCLC with 57% true positive results, CEA had the highest capacity (17%) to detect malignant lung tumours in general and adenocarcinomas of the lung with 29%. CYFRA 21-1 was dominant for squamous cell carcinomas (12%). Combining the four markers leads with the prerequisite of high specificity (> 99%) to 50% true positives for malignant lung tumours, 44% for NSCLC, 36% for squamous cell carcinomas, 53% for adenocarcinomas, and 78% for SCLC, respectively. In cases of lung tumours of unknown origin, the combined use of CEA, CYFRA 21-1, NSE and ProGRP is useful for the differentiation between benign and primary or secondary malignant disease and suggests the assignment to histological subtypes.