Alpha-fetoprotein: much more than a simple blood or cancer marker

Alfa-fetoproteina: molto più di un marker da dosare

Alpha-fetoprotein (AFP) is a well-known tumor marker and its production has been shown to correlate with the development of liver carcinoma, embryonal carcinoma, yolk sac tumors, teratocarcinoma, some testicular and ovarian tumors and hepatoblastoma. One of AFP’s most important functions is its immunosuppressive activity (Cardoso et al, 1991; Chakraborty and Mandal, 1993; Semeniuk et al, 1999), and this activity may be important in inhibiting cancer immunity during development. of the tumor. AFP induces the production of anti-proliferative and natural killer (NK) inhibitory factors in vivo, where a single injection of AFP in experimental animals leads to a 20% reduction in NK cell activity and the occurrence of increased activity spontaneous lymphocyte suppressor (NSL). Acceleration of tumor growth, decreased NK activity, and simultaneous increase in suppressor lymphocyte activity after AFP injection suggest that AFP suppresses immunity and facilitates tumor growth. These suppressive effects on antitumor immunity have been studied more than 30 years ago by Cohen et al. (1986). AFP inhibited the activation of NK lymphocytes stimulated with IL-2, interferon or synthetic poly-ribotids. This inhibitory effect did not depend on an increase in effector cell death or, in the case of interferon and polypibotides, of non-specific AFP binding to immunostimulants. The fact is that scholars agree in recognizing that AFP is produced by cancer cells, in order to get rid of the immune defenses of the individual.

Alpha-fetoprotein is also involved in some clinical aspects of a type of genetic anemia called Fanconi anemia (Lakhi NA et al. 2017). Fanconi anemia (FA) belongs to a family of genetic instability disorders that do not have the ability to repair DNA breaks. The lesion occurs at a decisive stage of mitosis (true division), allowing FA cells to ignore cell cycle arrest. The DNA repair pathways in FA depend on proteins called FANC (A-L). FANC proteins form large protein complexes with BRCA proteins and are involved in DNA repair. A compromised cascade in these events confers greater susceptibility to breast cancer in female patients. The diagnosis of Fanconi anemia is based on the association of congenital malformations, medullary insufficiency syndrome and hypersensitivity to chromosomal breaks induced by chemical agents. Increases in serum AFP have been reported in fetal and infantile anemia states, and multipotent stem cells in bone marrow are likely to be the source of AFP production in patients with AF. A study in 2000 showed that serum AFP levels were significantly higher (P <0.0001) in FA patients than non-FA aplastic patients (Cassinat B et al.). Serum AFP levels were analyzed from 61 patients with FA and 27 controls with acquired aplastic anemia or other inherited syndromes of the bone marrow. Serum AFP levels remained unchanged for at least 4 years of follow-up and allogeneic bone marrow transplantation did not change its levels. By contrast, the heterozygous parents of patients with AF had normal levels of AFP.

Other groups, independently, have hypothesized that AFP could have direct action on blood formation. At the end of the twentieth century, Bartha et al. (1999) evaluated the relationships between maternal serum AFP levels and various parameters that are analyzed during regular blood tests. These include fetal hemoglobin (HbF), hematocrit (Hct), red blood cell counts (RBC), mean corpuscular volume (MCV), mean hemoglobin value (MHC) and mean corpuscular hemoglobin concentration (MCHC) in 63 fetuses, 19 of with prenatal cordocentesis and 44 at elective cesarean section prior to labor. They also evaluated the relationships between fetal AFP and these same parameters, plus counts of erythroblasts, erythropoietin (EPO), serum iron, transferrin, ferritin, bilirubin, total protein and albumin in 51 umbilical cords immediately after delivery, in healthy and pregnant women complete. After adjustment based on gestational age, significant correlations were found between maternal AFP and fetal hemoglobin and hematocrit. There was also a significant negative correlation between fetal serum AFP and fetal red blood cells, hemoglobin, hematocrit, erythropoietin, and transferrin. Their data have concluded that alpha-fetoprotein could play a role in fetal erythropoiesis. This may be true not only for the formation of the fetal blood in pregnancy, but for the anemic state that almost always accompanies cancer patients. It is known today that other circulating factors may be responsible for the anemia that appears in cancer patients. But in the case of patients with AFP-producing tumors, this is likely to have a negative effect on their immunity and blood formation.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Bartha JL et al. J Reprod Med. 1999 Aug; 44(8):689-97.

Belyaev NN et al. Korean J Physiol Pharm. 2008;12:193-97.

Cassinat B et al. Blood. 2000 Aug 1; 96(3):859-863.

Cohen BL et al. Scand J Immunol. 1986 Feb;23(2):211-23.

Gorskaya YF et al. Bull Exp Biol Med. 2007;143(1):140-2.

Lakhi NA et al. Fetal Pediatr Pathol. 2017; 36(1):49-61.

Mizejewski GJ. Obstet Gynecol Surv. 2003; 58(12):804-26.

Informazioni su Dott. Gianfrancesco Cormaci 1111 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web e