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Alpha-Fetoprotein (AFP) is normally produced by the fetal gut, yolk sac, and liver.  It is important in the initial diagnosis of these tumors as well as monitoring the response of these tumors to chemotherapy. 

Common Association Liver, Germ cell tumors of the testis and ovary
Less Common Association Lung, Colon, Pancreas

Yolk sac tumors and alpha-fetoprotein in first year of life.

Brewer JA, Tank ES.

Department of Surgery, Oregon Health Sciences University, Portland.

Urology 1993 Jul;42(1):79-80 Abstract quote

Serum alpha-fetoprotein (AFP) levels are normally elevated in the first eight months of life. This is important information when using AFP as a tumor marker for patients in this age group.

We report a case of a one-month-old boy with a yolk sac tumor of the testis. After radical orchiectomy and a negative workup for metastatic disease, his AFP level dropped, but remained mildly elevated over the normal range for six months. Using a half-life of five days it was predicted that it would fall into this range in eighty days. Although the elevated levels suggested residual tumor, they did continue to decline each month which led us to pursue some other explanation for this pattern. A literature search revealed the AFP levels are normally elevated in this age group.

In retrospect, our patient's AFP was within this range less than sixty days after surgery. Dissemination of knowledge that the normal AFP ranges in young infants are higher than those in older patients will improve the clinical usefulness of AFP as a tumor marker in this age group.

Hereditary persistence of alpha-fetoprotein. Case report and review of the literature.

Schefer H, Mattmann S, Joss RA.

Department of Medicine, Kantonsspital, Luzern, Switzerland.

Ann Oncol 1998 Jun;9(6):667-72 Abstract quote

Persistently elevated alpha-fetoprotein (AFP) levels of 24 to 30 micrograms/ml (normal < 10 micrograms/ml) were found in a 38-year-old healthy man. Subsequently, AFP was found to be elevated in another five out of 13 family members within three generations.

The pedigree is consistent with an autosomal dominant inheritance pattern. No discernible disease and no functional abnormality appears to be associated with this clinically benign disorder which has been recorded in the literature on four occasions to date. The reported AFP levels in these other cases ranged from 18 to 198 micrograms/ml. Physiologically, AFP is mainly produced in the liver and the yolk sac of human fetuses more than four weeks old, with peak values of up to 4 mg/ml at 12 to 16 weeks of gestation. After birth, AFP levels usually fall, within eight to 12 months, to a very low concentration of < 10 micrograms/ml and persist at low levels throughout life. However, AFP levels can rise above normal in both children and adults in distinct conditions and diseases which will be discussed. Hereditary persistence of alpha-fetoprotein (HPAFP) should be considered in both children and adults with unexplained and persistent elevation of AFP e.g., those screened for hepatocellular carcinoma or diagnosed for germ cell tumor.

It should also be recognized in AFP screening for neural tube defects or Down's syndrome during pregnancy. Hereditary persistence of AFP can be easily confirmed by analyzing AFP levels in family members.

Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores.

Goldstein NS, Blue DE, Hankin R, Hunter S, Bayati N, Silverman AL, Gordon SC.

Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI 48073, USA.

Am J Clin Pathol 1999 Jun;111(6):811-6 Abstract quote

Patients with chronic viral hepatitis and cirrhosis often have elevated serum alpha-fetoprotein (AFP) values, the causes of which are unclear.

We studied 81 patients with chronic hepatitis C and the relationships of serum AFP and alanine aminotransferase (ALT) values, hepatic histologic features, and hepatocyte proliferation activity scores.

Twenty-two patients had nil to mild fibrosis, 34 had moderate fibrosis, and 25 had marked fibrosis-cirrhosis. The mean serum AFP value was significantly greater in patients with more fibrosis. Serum ALT values were slightly greater in the marked fibrosis-cirrhosis patient group. The differences in the HAI and in hepatocyte MIB-1 scores were not significant. Among all patients, increasing serum AFP values significantly correlated with increasing ALT values. However, there were no significant correlations with serum ALT or HAI and serum AFP values. There was no association between serum AFP values and immunohistochemical staining for AFP within hepatocytes.

These results suggest that elevated serum AFP values are the result of altered hepatocyte-hepatocyte interaction and loss of normal architectural arrangements. The presence of marked fibrosis or cirrhosis, a state of significant altered hepatocyte architecture, may be the underlying cause of increased serum AFP, rather than necrosis or active regeneration.

Alpha-fetoprotein variants in a case of pancreatoblastoma.

Chan MH, Shing MM, Poon TC, Johnson PJ, Lam CW.

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin.

Ann Clin Biochem 2000 Sep;37 ( Pt 5):681-5 Abstract quote

We describe a 6-year-old boy with histologically confirmed pancreatoblastoma and a markedly elevated serum alpha-fetoprotein (AFP) concentration.

Due to local tumour invasion, cytotoxic chemotherapy was given to debulk the tumour before attempting surgical resection. Serial serum AFP concentrations were measured on this patient. During chemotherapy there was a > 95% fall in total AFP. Tumour-specific variants of AFP, detected by isoelectric focusing, also disappeared during chemotherapy but recurred when chemotherapy was withdrawn. It is suggested that although there was no change in overall size of the tumour, as assessed by various imaging techniques, the changes in serological markers may indicate that the treatment did in fact cause considerable tumour necrosis, AFP and its variants may be useful markers of tumour response in patients with pancreatoblastoma.

The expression of AFP and its variants in pancreatoblastoma may be related to the embryonic origin of the pancreas.

Alpha-fetoprotein half-life as a predictor of residual testicular tumor. Effect of the analytic strategy on test sensitivity and specificity.

See WA, Cohen MB, Hoxie LD.

Department of Urology, University of Iowa Hospitals and Clinics, Iowa City 52242-1089.

Cancer 1993 Mar 15;71(6):2048-54 Abstract quote

BACKGROUND. Alpha-fetoprotein (AFP) serum values after orchiectomy for testicular cancer can be used to predict the residual disease status. However, the optimal strategy for postorchiectomy marker analysis has not been studied. This article evaluated different analytic methods in an effort to identify the approach that provided the greatest sensitivity and specificity for occult residual disease.

METHODS. Statistical information on the AFP half-life (t1/2) derived from a clinical data set of 24 patients with AFP-secreting clinical Stage A testicular cancer and pathologically defined nodal status was incorporated into a mathematic model of postorchiectomy marker values as a function of residual tumor volume and time. The model was used to test the effect of various analytic strategies on detecting the residual tumor. The clinical data set then was analyzed to measure the effect of different analytic methods on the predictive value of the AFP t1/2.

RESULTS. In the model, the AFP t1/2 calculated from a single set of serum measurements obtained from the initial serum t1/2 was a poor predictor of disease status in patients with up to 40% residual tumor volume. Determined by the sequential addition of serum values obtained at normal t1/2 intervals, the AFP t1/2 improved in sensitivity but required up to seven serial values (35 days) to detect an abnormal t1/2 in patients with 10% residual tumor. By contrast, changes in the most recent interval t1/2 relative to the initial calculated t1/2 predicted the disease status in patients with 10% residual tumor after four t1/2 (20 days) and in patients with 1% residual volume after 35 days.

CONCLUSIONS. The use of this last strategy in the clinical data set improved both the sensitivity and specificity of the AFP t1/2 in predicting residual tumor relative to the other methods.

Alpha-foetoprotein heterogeneity: what is its value in managing patients with germ cell tumours?

de Takats PG, Jones SR, Penn R, Cullen MH.

Queen Elizabeth Hospital, Birmingham, UK.

Clin Oncol (R Coll Radiol) 1996;8(5):323-6 Abstract quote

Alpha-foetoprotein (AFP) is widely used in the diagnosis, therapeutic monitoring and follow-up of patients with germ cell tumours. On occasion, the interpretation of a raised serum AFP measurement in a patient is confounded by the fact that AFP also increases in a variety of liver and gastrointestinal diseases. AFP exists as a number of isoforms, which can be separated by their differential binding to plant lectins. Thus, AFP-concanavalin A (ConA) binding affords a means of distinguishing between a raised AFP of teratoma or liver aetiology and has recently been reported to possess sensitivity and specificity approaching 100%.

We present a patient in whom column chromatographic ConA binding was used as a basis for clinical management decisions for treatment for relapsed germ cell testicular tumour. The presumption of high test specificity led to a delay in the diagnosis of cancer recurrence, from which the patient ultimately died.

We conclude that the clinical utility of lectin binding assays currently remains uncertain and further evaluation is warranted.

Alpha-fetoprotein in plasma and serum of healthy adults: preanalytical, analytical and biological sources of variation and construction of age-dependent reference intervals.

Christiansen M, Hogdall CK, Andersen JR, Norgaard-Pedersen B.

Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.

Scand J Clin Lab Invest 2001 May;61(3):205-15 Abstract quote

Alpha-fetoprotein (AFP) is a tumor marker for hepatomas and germ cell tumors, and the serum concentration has prognostic significance in other diseases.

We examined the normal serum concentration of AFP in adults and sources of variation in the immunochemical variation of AFP.

The serum concentration of the tumor marker alpha-fetoprotein (S-AFP) was log-normally distributed in 284 adult blood donors. S-AFP increased with age (p < 10(-7)), whereas no gender-related difference was found. Reference intervals (95-interpercentile) were constructed for persons < or =40 years (0.60-9.30 kIU/L) and >40 years (1.40 12.60 kIU/L). The concentration of AFP was significantly, albeit slightly, higher in serum than in plasma, whereas hemolysis, pretreatment with KCl and food intake did not influence S-AFP. S-AFP only changed 6% when measured twice 2 months apart (p=0.04). Three enzyme immunoassays, using three different anti-AFP monoclonal antibodies for detection, were compared and two assays gave S-AFP values significantly higher, 2.8% (p=0.03) and 19.0% (p<10(-4)), than the other assay. Thus, the choice of antibody may influence the result of immunochemical concentration determination. This can be explained by the existence of conformational variants of AFP with different antibody reactivities, and calls for careful standardization of monoclonal antibodies used in assays for AFP.

With broad population reference ranges and slight intra-personal variation, the most effective reference range for S-AFP is previous values obtained in the same person.

About 70% of patients with primary hepatocellular carcinoma and 50-70% of patients with nonseminiferous testicular tumors, have elevated serum AFP. Increases in the test value over time may indicate a recurrence in patients with a history of cancer.

In addition to its role in the diagnosis and management of malignancies, measurement of maternal serum and amniotic fluid levels play an important role in the screening for fetal neural tube defects and chromosomal abnormalities, including Down syndrome. Most measurements occur at 16 week gestation. There is maximal concentration within the fetal serum at this time, usually 3,000,000 ng/ml. Please visit our link to laboratory testing for pregnancy.

Am J Obstet Gynecol 1983;146:439-444.
Clin Cme 1986;32:1812-1817.
Clinical Diagnosis and Management by Laboratory Methods. 20th Edition. Henry JB. WB Saunders 2001.

Commonly Used Terms

MoM-Multiple of the median. This is determined by each screening program collecting the AFP medians for each week of pregnancy from 14-18 weeks by using at least 100 patients at each completed week (a patient at 16 weeks and 6 days will be included in the 16 week group). Patients whose results are greater than 3.5 standard deviations (SD) from the log mean are excluded. The estimates of the medians are plotted as a log-linear regression of AFP versus completed weeks of gestation. At 16 weeks of gestation, the typical median is 35 ng/ml. The patient's AFP concentration is divided by the median value appropriate for the patient's gestational age. Additional adjustments are made for insulin-requiring diabetes, maternal weight, maternal race, and number of fetuses. These AFP medians should be re-evaluated annually.

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Last Updated 1/5/2004

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