RESUMO
Background Measurement of α-fetoprotein (AFP) concentrations in the serum of infants is useful for the management of testicular germ cell tumors, hepatoblastoma and hepatocellular carcinoma. Here, we provide a critical review of the available information about pediatric reference intervals (RI), focusing on their utility in interpreting AFP as an aid for cancer diagnosis. Content Evidence sources in the available literature were critically appraised. Out of 3873 retrieved papers, 24 were finally selected and carefully inspected, and six of them overcame exclusion criteria (i.e. methodological limitations in the study design, statistical gaps, drawbacks in traceability of the AFP assay to higher order materials and/or biased reporting of AFP results). Preterm and term infants up to the 3rd month of life exhibited the highest average AFP concentrations, but the attempt of defining RI by data pooling and partitioning for age intervals was impeded by the wide variability of data. The inability of defining robust RI in the first months of life made difficult, if not impossible, using upper reference limits for ruling out malignancies with a single AFP result. Evaluating the behavior of AFP concentrations 5 days from the baseline result, if this exceeds risk thresholds partitioned for age, according to the formula Xt=X0*2-t/HL (where: t=days elapsed for AFP retest; HL=AFP half-life according to age; X0=AFP baseline concentration, and Xt=predicted AFP concentration at day 5), could give a better information. Summary Novel studies defining AFP RI in infants based on robust methodology are warranted to improve the interpretation of AFP results in pediatric oncology. In the meantime, algorithms based on both serum AFP absolute concentrations and HL may aid in cancer diagnosis.
Assuntos
Imunoensaio/métodos , alfa-Fetoproteínas/análise , Fatores Etários , Carcinoma Hepatocelular/diagnóstico , Hepatoblastoma/diagnóstico , Humanos , Imunoensaio/normas , Neoplasias Hepáticas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Valores de Referência , Fatores Sexuais , Neoplasias Testiculares/diagnóstico , alfa-Fetoproteínas/normasRESUMO
OBJECTIVES: Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study (ClinicalTrials.gov Identifier: NCT03047603). METHODS: This analysis included a total of 530 participants (41.43±12.14years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. RESULTS: AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0-7.07ng/mL (LOQ- 97.5th percentiles). CONCLUSIONS: The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults.
Assuntos
alfa-Fetoproteínas/análise , alfa-Fetoproteínas/normas , Adulto , Fatores Etários , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , China , Estudos Transversais , Etnicidade , Feminino , Humanos , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Padrões de Referência , Valores de Referência , Soro , Fatores SexuaisRESUMO
Objective: To establish a fetal biparietal diameter (BPD)-gestational age formula based on the data of pregnant women from Xiaoshan District of Hangzhou, and to evaluate its application in prenatal screening. Methods: Data of 3500 pregnant women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs were used to establish a localized BPD-gestational age formula. The localized formula was used to evaluate the prenatal screening risks in 1759 pregnant women with irregular menstrual cycles or uncertain last menstrual period (LMP) in Xiaoshan District, and the results were compared with those calculated using formula in LifeCycle 4.0. Results: With localized formula, the total positive rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was decreased from 6.96% to 5.85% ( P<0.05), in which the positive rate of Down syndrome decreased ( P<0.05), that of deformity of neural tube increased ( P<0.05), and that of trisomy 18 syndrome remained the same ( P>0.05). The median MoMs of free-hCG ß and α-fetoprotein calculated using localized formula were significantly different from those calculated using the formula in LifeCycle 4.0 (all P<0.05), and the former ones were more closer to 1. For women of fetus diagnosed with the above diseases, the positive rate calculated using localized formula was almost the same as that calculated using the formula in LifeCycle 4.0. Conclusion: BPD-gestational age formula should be localized based on the statistical analysis of the local population, which will help to reduce the false positive rate, and make the results more accurate and reliable in prenatal screening.
Assuntos
Pesos e Medidas Corporais/normas , Cefalometria/estatística & dados numéricos , Cefalometria/normas , Idade Gestacional , Cabeça/embriologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Diagnóstico Pré-Natal/estatística & dados numéricos , Diagnóstico Pré-Natal/normas , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Gonadotropina Coriônica Humana Subunidade beta/normas , Cromossomos Humanos Par 18 , Síndrome de Down/diagnóstico , Síndrome de Down/embriologia , Medidas em Epidemiologia , Feminino , Desenvolvimento Fetal , Humanos , Programas de Rastreamento/estatística & dados numéricos , Ciclo Menstrual , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/embriologia , Gravidez , Diagnóstico Pré-Natal/métodos , Valores de Referência , Trissomia/diagnóstico , Síndrome da Trissomía do Cromossomo 18 , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/normasRESUMO
Microvascular invasion (MVI) is well known to negatively influence outcomes following surgical treatment of hepatocellular cancer (HCC) patients. The aim of this study was to evaluate the rationale for prediction of MVI before liver transplantation (LT). Data of 200 HCC patients after LT were subject to retrospective analysis. MVI was present in 57 patients (28.5%). Tumor number (p = 0.001) and size (p = 0.009), and alpha-fetoprotein (p = 0.049) were independent predictors of MVI used to create a prediction model, defined as: 0.293x(tumor number) + 0.283x(tumor size in cm) + 0.164xloge(alpha-fetoprotein in ng/ml) (c statistic = 0.743). The established cut-off (≥2.24) was associated with sensitivity and specificity of 72%. MVI was not an independent risk factor for recurrence (p = 0.307), in contrast to tumor number (p = 0.047) and size (p < 0.001), alpha-fetoprotein (p < 0.001) and poor differentiation (p = 0.039). Recurrence-free survival at 5 years for patients without MVI was 85.9% as compared to 83.3% (p = 0.546) and 55.3% (p = 0.001) for patients with false negative and true positive prediction of MVI, respectively. The use of both morphological and biological tumor features enables effective pre-transplant prediction of high-risk MVI. Provided that these parameters are combined in selection of HCC patients for LT, pre-transplant identification of all patients with MVI does not appear necessary.
Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Microvasos/patologia , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/patologia , alfa-Fetoproteínas/normas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células Neoplásicas Circulantes/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/metabolismo , Valor Preditivo dos Testes , Carga TumoralRESUMO
BACKGROUND: Elevated alphafetoprotein (AFP) concentrations may result from a variety of clinical conditions, but their role as an important tumour marker has been well established. There may be differences in AFP values due to laboratories using different methods, even though most methods have been calibrated with the same international standard (WHO IS 72/225). Therefore it is important to know the analytical performance of the various methods in relation to the analytical requirements for AFP measurement. METHODS: Annually, from January 2005 to July 2010, the results were analysed from the 65-75 laboratories that took part in the AFP survey of the External Quality Assurance programme of the Foundation Quality Control Medical Laboratories (the SKML/Binding Analysis) in the Netherlands. RESULTS: The Elecsys/Modular (36%) and the Immulite 2000/2500 (29%) are the methods used most. The methods show, on average, up to 15% positive and 12% negative bias, compared with the all-laboratory trimmed mean. Of the laboratories using the Immulite or the Elecsys/Modular analyser, over 70% show sufficient analytical performance to meet the Fraser criterion for method imprecision. Of the laboratories using a different method, over 50% do not meet this criterion. CONCLUSIONS: AFP immunoassays suffer from method bias, even though all methods have been calibrated with the same international standard. Some of the methods used show insufficient performance.
Assuntos
alfa-Fetoproteínas/análise , Humanos , Laboratórios/normas , Países Baixos , Controle de Qualidade , Padrões de Referência , Manejo de Espécimes/normas , alfa-Fetoproteínas/normasRESUMO
Serum alpha-fetoprotein (s.AFP) has been established as a useful tool in monitoring of high-risk pregnancies, as an indicator of fetal neural tube defects, and has been used as an adjunct tumor marker and for monitoring therapeutic efficacy in the treatment of certain tumors. To date, the methods for measuring s.AFP are based upon the immunologic principle and are manual methods. The purpose here is to relate the evaluation of two automated systems for the assay of s.AFP. The automated systems are based upon the following immunoassay methods: a microparticle capture enzyme separation and final quantitation by reflectance fluorescence, and a solid phase 'sandwich' separation coupled with enzyme activity measurement (EIA). The reference method is a competitive binding radioimmunoassay. It has been found by us that the automated methods directly transfer analytically with the manual assay. All methods are referenced to the same standard (WHO 1st Intl. Std. for AFP 72/225).
Assuntos
Técnicas Imunoenzimáticas , Radioimunoensaio , alfa-Fetoproteínas/análise , Autoanálise , Ligação Competitiva , Feminino , Humanos , Técnicas Imunoenzimáticas/normas , Defeitos do Tubo Neural/diagnóstico , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/normas , Controle de Qualidade , Radioimunoensaio/normas , Reprodutibilidade dos Testes , alfa-Fetoproteínas/normasRESUMO
We have evaluated a new chemiluminescent substrate for the alkaline phosphatase (EC 3.1.3.1) label used in a Hybritech Tandem-E immunoassay of alpha-fetoprotein (AFP). The new substrate, adamantyl 1,2-dioxetane phenyl phosphate (AMPPD), emits light at 477 nm when acted upon by the enzyme. Detection limits for AFP with this method were 33 ng/L (mean of 20 replicates of the zero standard + 2 SD) and 470 ng/L (twice background). Between-batch CVs ranged from 4.31% to 9.60% for AFP in the range 29.1-132.0 micrograms/L. Comparison of results for 49 specimens assayed with use of the chemiluminescent kit and a colorimetric version of the AFP assay gave statistical values as follows: slope = 0.88, intercept = 4.19, and r = 0.94.
Assuntos
Adamantano/análogos & derivados , Fosfatase Alcalina , alfa-Fetoproteínas/análise , Líquido Amniótico/análise , Biomarcadores/análise , Colorimetria , Feminino , Humanos , Técnicas Imunoenzimáticas , Medições Luminescentes , Gravidez , Kit de Reagentes para Diagnóstico , Estatística como Assunto , alfa-Fetoproteínas/normasRESUMO
Starting from 1984 we organized an interlaboratory quality control (QC) survey for the tumor marker AFP in which 100-150 laboratories have been involved. Seven consecutive QC cycles have been carried out during the period 1984-1988; 15-20 samples have been prepared and sent in each cycle. The 11 kits more used in the survey, which use three different immunological methods (3 kits EIA, 3 kits RIA, and 5 kits IRMA) were evaluated. Since the results of AFP assays were expressed as ng/ml of different local standards of the various kits, the participants were asked to convert their results in UI/ml of the 1st IRP 72/225 distributed by WHO. The total variability of AFP assay resulted approximately constant (19.9-24.7 CV%) during the all QC period. The validity of the consensus mean of AFP determinations obtained in the survey and assumed as reference value has been checked by recovery experiments. Regression analysis indicates that the consensus means found in these samples are in very good agreement with the added AFP. The analytical performance achieved by the most popular methods/kits, observed in the last period, are also reported.
Assuntos
Laboratórios/normas , Kit de Reagentes para Diagnóstico/normas , alfa-Fetoproteínas/normas , Itália , Controle de QualidadeRESUMO
Sample-related background signals in immunoassays can be measured by a variation of the double antibody sandwich principle, in which the unlabelled specific antibody is substituted by a similar unrelated non-specific antibody. This permits differentiation between the analyte-specific and the background signal components for each sample. The method permits selection of sera with no or low analyte content for use as analyte diluent and for defining the zero point of the calibration curve. The method also permits control of analyte content during production processes which may change the background signal as well as identification of samples with atypical background signals. The procedure has been used for the calibration of enzyme immunoassays for alpha-fetoprotein (AFP) and human thyroid-stimulating hormone (TSH).
Assuntos
Calibragem/normas , Técnicas Imunoenzimáticas/normas , Pesos e Medidas/normas , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Sangue Fetal/análise , Humanos , Masculino , Camundongos , Padrões de Referência , Valores de Referência , Tireotropina/sangue , Tireotropina/normas , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/normasRESUMO
The human hepatoma cell line Hep G2 secretes both albumin and alpha-fetoprotein when grown in the presence of serum. The present report describes how adaptation to growth in serum-free medium results in a progressive switch in the expression of the two proteins; i.e., alpha-fetoprotein becomes the main protein secreted while albumin production is greatly reduced. The culture supernatant obtained, being very enriched in the protein, allows the development of a purification procedure by preparative electrophoresis. By this procedure it is possible to easily obtain large amounts of alpha-fetoprotein from a constant and unlimited source. The availability of these protein preparations should improve the reproducibility and the quality of standardization in clinical immunoassays for alpha-fetoprotein and should permit a more accurate study of the structure and biological functions of the protein.
Assuntos
Carcinoma Hepatocelular/metabolismo , alfa-Fetoproteínas/isolamento & purificação , Adaptação Biológica , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Humanos , Neoplasias Hepáticas , Células Tumorais Cultivadas/metabolismo , alfa-Fetoproteínas/normasRESUMO
Reagents (immobilized anti-alpha-fetoprotein discs) having a porous structure were prepared for enzyme immunoassay of alpha-fetoprotein by radiation polymerization at low temperatures. Discs were attached to sticks for easy handling. The activity (determined by absorbance at 492 nm) of the discs varied with the hydrophilic properties and size of the disc. The discs are sufficiently sensitive and precise for enzyme immunoassay of alpha-fetoprotein.