Alpha 1-fetoprotein Levels Research Articles

Highly Elevated Alpha-fetoprotein Concentration in a Premature Infant

Alpha-1-fetoprotein (AFP) is a protein produced by the liver. Although its biological function is not fully understood, it is often used as a marker for cancer. High levels of AFP are also observed in premature infants. Reference ranges for AFP levels in premature infants are not specified. The authors present a case of a male newborn born at 25+5/7 weeks of gestational age. The boy underwent oncological diagnostics due to the detection, on the 24th day of life, of a liver lesion in an abdominal ultrasound examination, as well as significantly elevated AFP levels (>430,000 ng/mL). With each passing day, the AFP level gradually decreased, and the suspicious lesion was not visualized on abdominal ultrasound or magnetic resonance imaging on the 59th day of life. Based on the conducted examinations, prematurity and its treatment were considered the cause of high AFP levels. The aim of the study was to present the diagnostic difficulties associated with the lack of AFP norms for premature infants.

Surgery in Infants and Children with Testicular and Paratesticular Tumours: A Single Centre Experience Over a 25-Year-Period

Testicular and even more paratesticular tumours in children are rare. The aim of the study is to characterise the spectrum of these lesions with focus on the feasibility and effectiveness of testis sparing surgery. Twenty-four boys treated between 1980 and 2004 at the University Leipzig Medical Centre were evaluated. At presentation patients were between 5 months and 18 years old (median 23 months). Generally a high rate of malignant or potentially malignant tumours was observed. The majority of these tumours occurred in the first three years of age. The spectrum of testicular tumours comprised 13 germ cell tumours (6 yolk sac tumours, 6 teratomas, 1 embryonal carcinoma) and 4 sex cord stromal tumours (2 Leydig's cell, Sertoli's cell, granulosa cell). Both Leydig's cell tumours were endocrine active. Further on, we observed 3 boys with paratesticular rhabdomyosarcoma (RMS), and three with testicular and paratesticular metastases (Wilms' tumour, neuroblastoma, leukaemia). Serum alpha1-fetoprotein (AFP) was clearly elevated in 5 of 6 yolk sac tumours but remained within normal limits concerning the other entities. Human chorionic gonadotrophin was normal in all cases tested. During the observation period high inguinal orchidectomy was the surgical standard method. Dependent on tumour histology, stage and the recommended treatment schedule postoperative chemotherapy was added. Testis sparing surgery was performed in 3 boys with primary testicular tumours (2 Leydig's cell, mature cystic teratoma). Local relapses were not observed. Systemic relapses occurred in 3 cases (2 RMS, leukaemia). During a median follow up of 5 years all patients with primary testicular tumours survived event free. Meta-analysis of the recent literature revealed that testis sparing surgery is feasible and save in prepubertal boys after exclusion of a malignant tumour. If a testis sparing approach is planned, the following criteria are essential: 1. The presence of a well defined circumscribed nodule confirmed by imaging. 2. Normal levels of serum AFP and hCG. 3. The presence of sufficient healthy testicular parenchyma. However, the high rate of malignant or potentially malignant tumours suggests that high inguinal orchidectomy should remain the surgical standard of therapy.

Antibodies against b2-GP I and their relationship to fetoplacental antigens

Binding of beta2-GP I to anionic phospholipids is thought to be the major antigen required in the reaction of anticardiolipin antibodies to phospholipids. The aim of this study was to investigate the changes of anti-beta2-GP I IgG during the first and second trimester of pregnancy and the relationship between the levels of anti-beta2-GP I and fetoplacental antigens and the correlation between anti-beta2-GP I IgG and antibodies against oxidized low-density lipoprotein IgG (oLAb) in serum of pregnant women. We determined anticardiolipin antibodies (ACA) IgG and maternal serum levels of alpha1-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and trophoblast-specific beta1-glycoprotein (SP1) in 204 pregnant women in the first and second trimester. From this group we selected 52 serum samples positive for ACA IgG and 16 samples negative for ACA IgG. In the samples of selected patients, the levels of anti-b2-GP I IgG and oLAb IgG were determined. Anti-b2-GP I IgG levels significantly decreased in the second trimester (6.2±9.3 U/ml, mean ± S.D.) in comparison with the first trimester (8.3±10.4 U/ml) (p=0.05). Multiple of median (MoM) AFP correlated negatively but not significantly in the first trimester with anti-b2-GP I (r = -0.261, p = 0.12). In the second trimester this correlation was significantly negative (r = -0.278, p = 0.04). The Spearman correlation coefficients for MoM HCG and anti-beta2-GP I were 0.158 for the first trimester and 0.174 for the second trimester. MoM SP1 also did not correlate significantly with anti-beta2-GP I in both trimesters. The correlation between anti-beta2-GP I IgG and oLAb IgG was not significant (r = -0.06). In the first trimester 40 % serum samples were positive for anti-b2-GP I IgG and negative for oLAb IgG or vice versa, while 60 % samples in the second trimester were positive only for one determined autoantibody. We can conclude that the levels of anti-beta2-GP I IgG decrease during the second trimester probably as the result of the effects of some immunosuppressive agents associated with pregnancy. The finding of negative correlation between AFP and anti-b2-GP I suggests that anti-b2-GP I has an influence on fetus development.

Alpha-1-Fetoprotein (AFP) und humanes Choriongonadotropin (hCG) in Seren schwangerer Frauen mit akuter Parvovirus-B19-Infektion mit und ohne fetale Komplikationen

Fragestellung und Methoden: In einer vorausgegangenen Studie (Komischke et al. [10]) mit 137 Seren von 65 Parvovirus-B19-infizierten Schwangeren konnten wir zeigen, daß weder Alpha-1-Fetoprotein (AFP) noch humanes Choriongonadotropin (hCG) im mütterlichen Serum verläßliche prognostische Marker für das Auftreten fetaler Komplikationen bei mütterlicher Parvovirus-B19-Infektion sind. Beide Marker sind allerdings häufig bei Auftreten der Komplikationen erhöht. In der vorliegenden Studie haben wir weitere 112 Seren von 59 schwangeren Frauen (30 mit, 29 ohne fetale Komplikationen) analysiert. Ergebnisse: Bei den 30 Schwangeren mit fetalen Komplikationen waren im mütterlichen Serum in 10 der 30 Fälle AFP und hCG gleichzeitig erhöht, in 6 Fällen war nur das hCG und in einem der 30 Fälle nur das AFP deutlich erhöht. Bei den 29 Schwangeren ohne fetale Komplikationen war in einem Fall AFP und hCG gemeinsam und in 6 Fällen nur das hCG erhöht. Schlußfolgerung: Damit bestätigen sich unsere früheren Ergebnisse, daß ein Hydrops fetalis und/oder der Verlust der Feten als Folge einer Parvovirus-B19-Infektion zwar häufig mit Erhöhungen des hCG und weniger häufig mit der Erhöhung von AFP im mütterlichen Serum assoziiert sind. Dennoch sind beide keine verläßlichen Frühmarker für die Vorhersage fetaler Komplikationen bei Parvovirus-B19-infizierten schwangeren Frauen. Zur Erkennung von Frühzeichen einer fetalen Gefährdung (beginnender Hydrops) wird die engmaschige sonographische Überwachung der Parvovirus-B19-infizierten Schwangerschaft empfohlen. Die farbkodierte Dopplersonographie kann auch Hinweise auf das Vorliegen einer fetalen Anämie geben, so daß invasiv-diagnostische und therapeutische Maßnahmen eingeleitet werden können.

Alpha1-Fetoprotein (AFP) Reference Values in Infants up to 2 Years of Age

The aim of this study was to establish reference values and factors associated with serum AFP elevation in infants. Five hundred twenty-four samples collected from infants up to the age of 2 years at the University Hospital Düsseldorf (Germany) were analyzed. At birth mean serum AFP levels were 41,687 ng/ml in 256 term babies and 158,125 ng/ml in 90 premature babies born before the 37th gestational week, excluding samples from children with factors known to be associated with AFP elevation. In the first 4 weeks of life, AFP levels decreased by 50% in 5.1 days in term babies. Between day 180 and 720 of life, AFP levels up to 87 ng/ml were within the 95.5% interval (assumed logarithmic normal distribution) with a mean of 8 ng/ml without a further decline. By the age of 2 years the infants of this study had not reached adult serum AFP levels (0-6 ng/ml).

Pancreatoblastoma in children. Case report and review of the literature.

Pancreatolblastomas are rare embryonal malignancies in childhood. We report a 3-year-old girl with a tumor of the head of pancreas. Staging by bone scintigraphy and CT scans of abdomen and chest did not show evidence of metastatic disease. Tumor markers showed elevated levels of alpha-1 fetoprotein (64 ng/ml; normal 0-10 ng/ml) and lactate dehydrogenase (423 U/l; normal range below 300 U/l). The tumor was macroscopically completely removed by local resection. Postoperative tumor grading was pT1, NO, MO. The child recovered very soon after surgery without severe complications. Tumor markers dropped to normal values, indicating complete remission (follow-up time 12 months). According to the biological growth characteristics of pancreatoblastomas and to the literature, localized and non-metastatic tumors should be completely resected without radical pancreatoduodenectomy and without adjuvant chemotherapy. This is the most conservative therapy with a good prognosis. However, metastatic disease, primarily inoperable conditions or local relapses are indications for chemotherapy combined with radiotherapy and followed by resection of the tumor. At present, the prognosis of such cases is rather poor.

Hepatic artery injection of I-131-labeled lipiodol. Part II. Preliminary results of therapeutic use in patients with hepatocellular carcinoma and liver metastases.

Internal radiation therapy with transarterial injection of iodine-131-labeled iodized oil (Lipiodol Ultra-Fluide [LUF]) was evaluated in 15 patients with hepatocellular carcinoma and eight with hepatic metastases. Five patients with hepatocellular carcinoma received more than one injection. Treatment tolerance was excellent, as assessed clinically and by means of liver function tests. An analgesic effect was noted in the two patients with painful hepatocellular carcinomas. Serum alpha 1-fetoprotein levels dropped rapidly in 11 of the 12 patients with elevated basal values. An average reduction in tumor size of 50% was observed in the nine cases followed up with computed tomography. After 5-12 months of follow-up, six of the 15 patients with hepatocellular carcinoma were alive. Two of them had undergone liver transplantation. Histologic examination of one of the livers, removed 3 months after a third injection, revealed microscopic features highly suggestive of radiation effect in LUF-containing areas. In the group with widespread hepatic metastases, no objective response was noted, except for an analgesic effect in three cases.

Guinea-pig alpha 1-fetoprotein: purification, characterization, developmental and hormonal regulation, and behavior in diethylnitrosamine hepatocarcinogenesis.

Physicochemical and immunological procedures were developed for the purification of guinea-pig alpha 1-fetoprotein (AFP). A double-antibody radioimmunoassay was developed which can detect 0.1 ng of AFP. The E1%278 nm of guinea-pig AFP is 6.6. Its molecular weight is 73 000. Its amino acid composition is similar to other AFP's, but it has a higher carbohydrate content (8.5%), owing to larger amounts of mannose and N-acetylglucosamine. Guinea-pig AFP has a slower electrophoretic mobility than other AFP's, owing to its more basic ionic structure. It separates into three electrophoretic variants in nondenaturing polyacrylamide gels; these are charge variants with isoelectric points of 5.0, 5.12, and 5.54. Changes in electrophoretic mobility after neuraminidase treatment indicate that charge heterogeneity is due to a variable content in sialic acid. Guinea-pig AFP has fatty-acid- and lectin-binding properties, but no affinity for sex hormones. Its biological half-life is 2.1 days. Its sites of synthesis are the liver and the yolk sac, with minor contributions by the upper gastrointestinal tract. AFP production appears to cease synchronously in the liver and yolk sac during the 8th week of gestation. From 4 to 8 weeks of gestation, AFP levels are at 2.5-3.5 mg/mL in fetal serum and 0.1-0.2 mg/mL in amniotic fluid. The proportion of electrophoretic and lectin-reactive AFP variants changes during development, reflecting the changing glycosylation of the protein. The gestational levels of AFP in the maternal compartment are indicative of a fetomaternal equilibration through transamniotic exchange. Serum AFP levels in normal adult guinea pigs are remarkably high, from 400 to 2000 ng/mL and occasionally up to over 5000 ng/mL. The administration of dexamethasone suppresses serum AFP levels. During liver carcinogenesis induced by diethylnitrosamine, serum AFP levels increase, moderately, when tumors develop.

Synthesis of alpha-fetoprotein by the pre-implantation and post-implantation bovine embryo.

The synthesis of alpha 1-fetoprotein (AFP) was measured by radioimmunoassay in tissues and fluids of 19 bovine embryos (14-46 days of gestation) and in tissue cultures of 4 pre-implantation embryos (17-27 days) by incorporation of radioactive methionine. AFP was first detected in Day-14 trophoblasts and secretion of AFP into allantoic fluid occurred by Day 16. Embryonic tissues and fluids in pre-implantation and post-implantation embryos contained levels of AFP that were 550 to 1 500 000 times higher than those found in maternal serum (3.9-298 000 compared with 0.07-0.25 ng/mg protein). High levels of AFP were also found in uterine fluid which suggested significant transfer of this protein from the early post-implantation conceptus. The major sites of AFP synthesis were yolk sac and fetal liver. It is concluded that the synthesis of bovine AFP is not initiated by events associated with implantation.

Alpha-fetoprotein: cellular origin of a biological marker in rat liver under various experimental conditions.

Alpha1-fetoprotein (AFP) was detected by serological, light and electron microscopic methods in various experimental models. These included (a) liver regeneration after partial hepatectomy or CCl4 intoxication (mouse and rat); (b) liver intoxication by high doses of N-nitrosomorpholine (NNM) and chemical induction of hepatomas (rat). AFP levels varied greatly according to the animal species and strains used. Low and high AFP-producing species and strains were distinguished. In liver regeneration after hepatectomy or CCl4 intoxication, cellular AFP was found in the cytoplasm of hepatocytes. In NNM-intoxicated livers, elevated AFP levels were associated with proliferation of canalicular epithelial cells in which AFP was localized. In early stages of hepatocarcinogenesis, significant AFP increase occurred after high-dose carcinogen feeding and AFP was also localized in proliferating canalicular epithelial cells. On low-dose NNM feeding, no cellular AFP was detected unless hepatomas had developed. At the stage of malignant conversion, distinct AFP staining and non-AFP staining hepatocellular carcinomas appeared in livers.

Immunoperoxidase labelling of alpha 1-fetoprotein (AFP) in normal and regenerating livers of a low and a high AFP producing mouse strain.

Serum AFP concentrations in normal adult BALB/c/J and in normal adult C3H/He mice were in the order of 0.6 μg/ml and 0.1 μg/ml, respectively. In BALB mice, AFP was localized in the cytoplasm of differentiated mono- and binucleated hepatocytes in centrolobular and intermediate zones of normal adult liver. No cellular AFP could be detected in liver sections of normal adult C3H mice. CCl4 intoxication was accompanied by increase of serum AFP levels. A maximum was reached on day 4. Afterwards, concentrations declined. In sera of BALB/c/J mice, AFP levels reached values 10-fold higher and more than in sera of C3H/He mice. From day one after CCl4 intoxication, cellular AFP was detected in hepatocytes of portal and periportal areas including intermediate zones adjacent to the necrosis. The intensity of AFP staining reached a maximum between the days 3 and 4. Hepatocytes in front of the necrotic areas usually contained the strongest AFP reactions. In both mouse strains, cellular AFP pattern was comparable, but strongest immunoreactivity was observed in liver sections of BALB/c/J mice. Liver injury and subsequent regeneration occurred to the same extent in both studied strains. The much higher serum AFP levels and the stronger AFP immunolocalizations in BALB mice were thought not due to increased numbers of AFP producing and releasing cells during liver regeneration. Additional mechanisms must play a role in increased AFP synthesis per single cell. C3H/He was a low AFP-inducible and BALB/c/J was a high AFP-inducible mouse strain.

Alpha‐fetoprotein Determination: A Warning

Alpha‐1‐fetoprotein (AFP) was determined by different immunochemical techniques in the serum of a patient with liver cirrhosis. Although a precipitation line was observed against anti‐AFP antiserum, using bidimensional immunodiffusion, immunoelectrophoresis, countercurrent electrophoresis and rocket electrophoresis, this precipitation line however showed a reaction of non‐identity with a positive AFP control. Several different commercial anti‐AFP antisera gave the same false‐positive result. Analysis of the patient's serum revealed the falsely positive reacting component to be of IgM‐like nature, having a cathodal mobility. These findings are discussed in the light of the determination of slightly elevated AFP levels by a method such as the radioimmunoassay, not allowing identification by means of identity with control specimen. The consequence of our results is also discussed with respect to normal serum AFP.The described non‐AFP activity was detected regularly in sera taken over the period 1969–1976.

Localization of alpha1-fetoprotein and DNA-synthesis in liver cell populations during experimental hepatocarcinogenesis in rats.

AbstractSix‐, 12‐ and 20‐week‐old rats were fed N‐nitrosomorpholine (NNM) at low concentrations (6 mg/kg/day) or high concentrations (20 mg/kg/day) for 6 or 12 weeks. Irrespective of the age of the rats, both NNM schedules resulted in development of hepatomas and during the early stages of hepatoma induction, liver histotoxic patterns depended only on the dose of carcinogen employed. Necrosis of hepatocytes and proliferation of small, oval‐shaped cells occurred when high doses of NNM were applied. Parallel to the proliferation of oval‐shaped cells, resurgence of alpha1‐fetoprotein (AFP) in rat sera was observed and production of this protein was confined to the oval‐shaped cells as shown by immunoperoxidase staining. During proliferation of bile duct epithelium, induced by galactosamine injections, those cells could also stain for AFP, and proliferation of oval‐shaped cells concomitant with intracellular AFP staining resulted from restitution of heavily damaged liver. In pulse‐chase labelling experiments with 3H‐thymidine, oval‐shaped cells were seen in continuous development towards hepatocytes, and distinct areas of hyperplastic appearance occurred. Normal hepatocytes and hyperplastic areas did not stain for AFP. Upon low‐dose feeding of NNM, no cellular AFP and no serum AFP were detected unless hepatoma cells had developed. At the stage of malignant conversion, distinct AFP‐staining nodules were localized which consisted of neoplastic hepatocytes. AFP‐staining and non‐AFP‐staining nodules were seen concomitantly in the same animal. AFP was localized only in neoplastic hepatocytes. Pulse‐labelling experiments with [3H]thymidine showed the proliferative character of hepatoma cells from which the AFP‐staining population in particular was involved. No correlation was found between the presence of AFP and histological grading of hepatomas. The wide range of both serum AFP levels and their rising rates in individual rats indicated the highly heterogeneous character of the induced hepatomas with respect to AFP production.

Amniotic fluid alpha1fetoprotein in the diagnosis of neural tract malformations.

Amniotic fluid alpha1fetoprotein levels were determined in 400 pregnancies. The normal range for alpha1fetoprotein in amniotic fluid was defined by 350 samples from normal pregnancies. Elevated levels of alpha1fetoprotein were detected in 17 out of 18 pregnancies which gave rise to infants with neural tract abnormalities. The significance of this test in the antenatal diagnosis of neural tract abnormalities is discussed together with the possible reasons for "false negative" and "false positive" results. There were no complications in an individual series of 105 consecutive amniocenteses.

Influence of gestational age on serum levels of alpha-1 fetoprotein, IgG globulin, and albumin in newborn infants

Alpha-1 fetoprotein, IgG globulin, and albumin concentrations in the serum of 153 newborn infants were correlated with gestational age (length of pregnancy). Neonatal levels of alpha-1 fetoprotein fell, while those of IgG and albumin rose, as gestational age increased. Thus the levels of alpha-1 fetoprotein are inversely proportional to gestational age (r=−0.81, p

Evaluation of human gestational age by albumin, IgG globulin, and alpha-I-fetoprotein measurements

Serum albumin (Alb) and IgG globulin levels in the developing fetus increase with maturity because of an increasing placental passage from the maternal circulation to the fetus. In contrast, levels of alpha-1-fetoprotein (AFP) decrease with maturity from a maximum serum level at 20 weeks of gestation (mean level > 140.0 mg%) to trace levels (mean 5 mg%) at 40 weeks gestation. These observations permit an estimation of gestational age by measuring levels of cord blood IgG, Alb, and AFP, and when paired maternal IgG and Alb levels are available, by calculating fetal/maternal IgG and Alb ratios. Cord sera (and the matfhed maternal sera) from 55 infants (23 preterm, 32 term) on whom gestational age had been estimated by maternal history and physical examination (Dubowitz criteria, J. Ped. 77:1, 1970) were studied. Gestational age was correlated (p < .001) directly with cord levels of IgG (r = 0.81) and Alb (r = 0.73) and AFP (r –0.76). Using a fetal/maternal IgG and Alb ratio did not result in an improved correlation. Although AFP was detected in all cord sera, AFP was not detected in the maternal circulation, nor in 14 of 15 amniotic fluid samples. Cord IgG and albumin levels best reflect gestational duration while cord AFP levels reflect fetal maturity.