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Alpha-Fetoproteins: Structure, Functions and Health Implications (pp.173-188) $0.00
Authors:  (Roberta Elisa Rossi, Sara Massironi, Dario Conte, Gastroenterology Unit II, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milano, Italy, and others)
Abstract:
Alpha-fetoprotein (AFP) is a glycoprotein of 591 amino acids, encoded by the AFP gene, which is produced by the yolk sac, the fetal gastrointestinal tract and the fetal liver. Levels of AFP in fetal serum rise until the end of the first trimester of gestation and then fall: in fact, AFPs expression is usually repressed in adults. The protein is thought to be the fetal counterpart of serum albumin and it is found in monomeric as well as dimeric and trimeric forms. It binds copper, nickel, fatty acids and bilirubin. Some studies suggest that AFP may also act as a regulator of cell growth and survival.
AFP serum levels are raised in several clinical conditions, ranging from non-pathological conditions to malignancies. In evaluating an elevation in maternal serum AFP, it is first necessary to consider the amount of fetal production by confirming the gestational age of the fetus and the number of fetuses present. Adjustments for maternal factors (i.e. weight, race, diabetes) should also be made. Furthermore, the presence of an abnormal placenta could be responsible for a greater amount of AFP being transported to the maternal circulation.
However, AFP is a marker for certain cancers and congenital defects. First, the AFP test is a screening test, which is routinely used: AFP is drawn from maternal blood
usually between 15-17 weeks gestation, helping to diagnose babies who suffer from neural tube defects or Down Syndrome.
Moreover, elevated levels of AFP occur on the development of germ cell tumors, including yolk sac tumor and embryonal carcinoma of the ovary. Rarely, other tumors of the female genital tract produce AFP, such as different types of carcinomas and carcinosarcomas of the uterus and cervix and sex cord stromal tumors of the ovary.
AFP has always been known as a serum marker for hepatocellular carcinoma (HCC). Interestingly, patients with chronic liver disease, particularly in case of high rate of hepatocyte regeneration, can express AFP in the absence of cancer. Also, AFP could be elevated in gastric and lung cancer. According to previously published studies, the test had a sensitivity of 39%-65%, a specificity of 76%-94%, and a positive predictive value of 9%-50% for the presence of HCC. Moreover, AFP seems to be of prognostic value at the time of tumor diagnosis: a high AFP concentration (≥ 400 ng/mL) in HCC patients is associated with greater tumor size, bilobar involvement, portal vein invasion, and a lower median survival rate, while well-differentiated tumors express lower levels of AFP. In addition, AFP could be used either as a marker for detecting tumour progression in patients with AFP-producing cancers or as an excellent marker for detection of de novo HCC after treatment.
Finally, in patients with unexplained elevated AFP levels, hereditary persistence of alpha-fetoprotein (HPAFP), a benign autosomal dominantly inherited condition not associated with any clinical implication, should be taken into consideration. 


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Alpha-Fetoproteins: Structure, Functions and Health Implications (pp.173-188)