Wednesday 21 September 2011

Alpha Feto Protein

Clinical Significance

AFP is produced by the fetus primarily in cells of the yolk sac,GI tract and liver.AFP appears as a major serum protein in the fetus but its concentration decrease rapidly towards birth.The reappearance of elevated AFP concentrations in adult serum has been observed not only during pregnancy but also in conjunction with several benign and malignant.

AFP in Pregnancy

AFP concentrations in fetal serum decline after 2 nd trimester to reach the trace concentrations found in normal adults 18 x months after birth.AFP is detectable in amniotic fluid and maternal blood at 10-12 weeks gestation.Screening for AFP should occur at15-20 weeks gestation(optimum 16-18 weeks), as concentrations are rising rapidly at this time.A positive AFP result means that the amount of AFP in maternal blood is greater or less than that usually seen.It does not necessarily mean that a birth defect is present.Results are expressed in ng/mL and as "multiples of the median"(MoM).the most common cause for elevated AFP is inaccurate dating of pregnancy.A high AFP can also signal the presence of twins(50% are detected).Most important,however,are neural tube defects,present in 1-2/1000 babies.These defects include anencephaly(95% detected) and spina bifida(70-85% detected)

Neural tube defects are caused by failure of neural tube fusion,leading to permanent developmental defects of the brain or spinal cord or both. In most cases,there is no skin to cover the opening,so fetal serum AFP gains access to the amniotic fluid in large concentrations.The AFP then passes from amniotic fluid to maternal blood,where it is detected in increased quantities.In addition,neural tube defects tend to appear at random,with no established familial link or family history,further reinforcing the need for prenatal AFP screening.Low AFP values also include inaccurate dating of pregnancy,and most importantly,fetal Down syndrome.Down syndrome occurs in 1/800 of live births.AFP values are usually 30% lower in mothers with fetuses having Down syndrome,independent of the mother's age.

Clinical application

AFP levels decrease soon after birth; AFP probably has no normal function in adults.

AFP is measured to :

  • Diagnose or monitor fetal distress or fetal abnormalities
  • Diagnose some liver disorders
  • Screen for and monitor some cancers.(eg: nonseminomatous testicular cancer)
Tumor marker for hepatoma :
  1. Screening in high prevalence areas. A cut-off point of 10-20 lU/ml has been recommended (after ruling out hepatitis and cirrhosis) in 50% of the patients.AFP levels > 1000 ng/ml usually indicates a tumor rise more than 3 cms in diameter.Increased in almost 100 % of children and young adults with such tumors.90% of patients with hepatoma have AFP concentrations of >200ng/ml.
  2. Monitoring the rate of AFP clearance from the serum after treatment is an indicator of the effctiveness of the therapy.Conversly the growth rate of progessive  cancer can be monitored by serially measuring serum AFP concentrations over time.
  3. Useful as prognostic indicator of survival.
  4. Patients with chronic active hepatitis (CAH) or cirrhosis,positive for HbsAg should be screened every 4-6 months with serum AFP and ultrasound studies.
Tumor marker for germ cell tumors of Ovary and testes.
  1. AFP in combination with HCG forms a major tool in detecting and differential diagnosis of the germ cell tumors.90% of patients with non-seminomas with non-seminotous testicular tumors are positive for AFP and HCG or both.
  2. AFP is elevated in yolk sac tumors where as HCG is elevated in choriocarcinoma
  3. AFP is not incresed in pure seminomas without leutomatous component.
  4. Is used for monitoring treatment for recurrence and progression of the tumors.It also correlate with the tumor volume.
The screening for fetal defects and fetal disease during pregnancy

May be used along but generally used in combination with BetaHCG and UE3 as triple marker test for evaluation of fetal well being and detection of genetic fetal defects  early in the pregnancy.

Useful in distinguishing neonatal hepatitis(most patients have concentration of >40 ng/ml from biliary atresia.Most patients have concentrations of <40 ng/ml.

Elevated in
  • Cancer in testes,ovaries ,biliary(liver secretion)tract,stomach,or pancreas
  • Cirrhosis of the liver
  • Liver Cancer
  • Malignant teratoma
  • Recovery from hepatitis
  • Ataxia telangiectasia
  • Hereditary tyrosinemia
During pregnency,increased levels of AFP may indicate:
  • fetal defects
  • Spina bifida
  • Anencephaly
  • Omphalocele
  • Tetralogy of Fallot
  • Duodenal atresia
  • Turner's syndrome
  • Intrauterine death(usually results in a miscarriage)
Additional conditions under which the test may be performed:

  • Testicular cancer
Absent in
  • Normal persons after first few weeks of life
  • Various types of cirrhosis and hepatitis in adults
  • Seminoma of testis
  • Choriocarcioma,adenocarcinoma and dermoid cyst of ovary.
Limitations
APP measurements are not recommended as a screening procedure to detect cancer in the general population.the occurrence of elevated serum AFP levels in conditions other than nonseminomatous testicular cancer precludes the use of AFP measurements in the diagnosis of nonseminomatous testicular cancer.