AFP-L3

Last updated

In oncology, AFP-L3 is an isoform of Alpha-fetoprotein (AFP), a substance typically used in the triple test during pregnancy and for screening chronic liver disease patients for hepatocellular carcinoma (HCC). AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3 based on the reactivity with the lectin Lens culinaris agglutinin (LCA). AFP-L3 binds strongly to LCA via an additional α 1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine; this is in contrast to the L1 isoform. It is the L1 isoform which is typically associated with non-HCC inflammation of liver disease condition. The L3 isoform is specific to malignant tumors and its detected presence can serve to identify patients whom need increased monitoring for the development of HCC in high risk populations (i.e. chronic hepatitis B & C and/or liver cirrhosis). AFP-L3% is now being considered as a tumor marker for the North American demographic.

AFP-L3% assay

AFP-L3 is isolated via an immunoassay and quantified using chemiluminesence on an automated platform. Results for AFP-L3 are represented as a ratio of LCA-reactive AFP to total AFP (AFP-L3%). The AFP-L3% assay, a liquid-phase binding assay, will help to identify at-risk subjects earlier, allowing for more intense evaluation for evidence of HCC according to existing practice guidelines in oncology. AFP-L3% is the standard for quantifying the L3 isoform of AFP in serum of high risk chronic liver disease (CLD) patients. Studies have shown that AFP-L3% test results of more than 10% can be indicative of early HCC[ citation needed ] or early nonseminomatous germ cell tumor. [1]

Early testimonials from hepatologists indicate that there is a target patient population for the AFP-L3% assay. This target population are those CLD patients who have AFP concentrations in the indeterminate range of 20-200+ ng/mL and a small or indeterminate mass on imaging. It is in this range that doctors experience trouble differentiating non-HCC fluctuations in AFP vs indication of HCC. In such patients these hepatologists recommend utilizing AFP-L3% to clarify the disease state. Some hepatologists also use a positive result to urge insurance companies to pay for more frequent and intensive imaging.

Ultimately AFP-L3% may be used as a rule-in or rule-out assay for transplantation consideration and/or an intermediate step in surveillance precluding costly imaging on patients with fluctuating AFP results but negative for HCC.

Related Research Articles

Hepatocellular carcinoma Medical condition

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

Alpha-fetoprotein Fetal analogue of serum albumin

Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene. The AFP gene is located on the q arm of chromosome 4 (4q25). Maternal AFP serum level is used to screen for Down syndrome, neural tube defects, and other chromosomal abnormalities.

Liver tumors are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as benign (non-cancerous) or malignant (cancerous) growths. They may be discovered on medical imaging, and the diagnosis is often confirmed with liver biopsy. Signs and symptoms of liver masses vary from being asymptomatic to patients presenting with an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction. Treatment varies and is highly specific to the type of liver tumor.

Hepatoblastoma Liver cancer occurring in infants and children

Hepatoblastoma is a malignant liver cancer occurring in infants and children and composed of tissue resembling fetal liver cells, mature liver cells, or bile duct cells. They usually present with an abdominal mass. The disease is most commonly diagnosed during a child's first three years of life. Alpha-fetoprotein (AFP) levels are commonly elevated, but when AFP is not elevated at diagnosis the prognosis is poor.

Des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence/antagonist-II (PIVKA-II), is an abnormal form of the coagulation protein, prothrombin. Normally, the prothrombin precursor undergoes post-translational carboxylation by gamma-glutamyl carboxylase in the liver prior to secretion into plasma. DCP/PIVKA-II may be detected in people with deficiency of vitamin K and in those taking warfarin or other medication that inhibits the action of vitamin K.

Alpha-enolase Protein-coding gene in Homo sapiens

Enolase 1 (ENO1), more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase, in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy.

Liver cancer Medical condition

Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.

Glypican 3 Protein-coding gene in the species Homo sapiens

Glypican-3 is a protein that, in humans, is encoded by the GPC3 gene. The GPC3 gene is located on human X chromosome (Xq26) where the most common gene encodes a 70-kDa core protein with 580 amino acids. Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).

CKLF (gene)

Chemokine-like factor (CKLF) is a member of the CKLF-like MARVEL transmembrane domain-containing family of proteins that in humans is encoded by the CKLF gene. This gene is located on band 22.1 in the long arm of chromosome 16.

Fibrolamellar hepatocellular carcinoma Medical condition

Fibrolamellar hepatocellular carcinoma (FHCC) is a rare form of hepatocellular carcinoma (HCC) that typically affects young adults and is characterized, under the microscope, by laminated fibrous layers interspersed between the tumour cells. Approximately 200 new cases are diagnosed worldwide each year.

Selective internal radiation therapy

Selective internal radiation therapy (SIRT), also known as transarterial radioembolization (TARE), radioembolization or intra-arterial microbrachytherapy is a form of radiation therapy used in interventional radiology to treat cancer. It is generally for selected patients with surgically unresectable cancers, especially hepatocellular carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor, where the spheres lodge in the small vessels of the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue is called chemoembolization, of which transcatheter arterial chemoembolization (TACE) is the usual form.

Ramucirumab is a fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.

Yttrium-90 is an isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer.

In transplantation medicine, the Milan criteria are set of criteria applied in consideration of patients with cirrhosis and hepatocellular carcinoma (HCC) for liver transplantation with intent to cure their disease. Their significance derives from a landmark 1996 study in 48 patients by Mazzaferro et al which showed that selecting cases for transplantation according to specific strict criteria led to improved overall and disease-free survival at a four-year time point. These same criteria have since been adopted by the Organ Procurement and Transplantation Network (OPTN) in the evaluation of patients for potential transplantation.The threshold Milan criteria are as follows:

Elevated alpha-fetoprotein refers to a state where alpha-fetoprotein levels are outside of the reference range.

Patrizia Paterlini-Bréchot, born in the Italian city of Reggio Emilia, is an Italian scientist and a professor of cell biology and oncology working at the Faculté de Médecine Necker-Enfants Malades, Université Paris Descartes and at INSERM in Paris.

Brivanib alaninate Chemical compound

Brivanib alaninate (INN/USAN) also known as BMS-582664 is an investigational, anti-tumorigenic drug for oral administration. The drug is being developed by Bristol-Myers Squibb for the treatment of hepatocellular carcinoma or HCC, the most common type of liver cancer.

Resminostat is an orally bioavailable inhibitor of histone deacetylases (HDACs), of which inhibitors are antineoplastic agents.

Ultrasonography of liver tumors involves two stages: detection and characterization.

Transarterial bland embolization is a catheter-based tumor treatment of the liver. In this procedure, a variety of embolizing agents can be delivered through the tumor’s feeding artery in order to completely occlude the tumor’s blood supply. The anti-tumor effects are solely based on tumor ischemia and infarction of tumor tissue, as no chemotherapeutic agents are administered. The rationale for the use of bland embolization for hepatocellular carcinoma(HCC) and/or other hyper-vascular tumors is based on the fact that normal liver receives a dual blood supply from the hepatic artery (25%) and the portal vein (75%). As the tumor grows, it becomes increasingly dependent on the hepatic artery for blood supply. Once a tumor nodule reaches a diameter of 2 cm or more, most of the blood supply is derived from the hepatic artery. Therefore, bland embolization and transarterial chemoembolization (TACE) consist of the selective angiographic occlusion of the tumor arterial blood supply with a variety of embolizing agents, with or without the precedence of local chemotherapy infusion. The occlusion by embolic particles results in tumor hypoxia and necrosis, without affecting the normal hepatic parenchyma.

References

  1. Kamoto T, Satomura S, Yoshiki T, Okada Y, Henmi F, Nishiyama H, Kobayashi T, Terai A, Habuchi T, Ogawa O (2002). "Lectin-reactive alpha-fetoprotein (AFP-L3%) curability and prediction of clinical course after treatment of non-seminomatous germ cell tumors". Jpn. J. Clin. Oncol. 32 (11): 472–6. doi: 10.1093/jjco/hyf094 . PMID   12499420.
  1. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Li D, et al., Clin Chim Acta. 2001 Nov;313(1-2):15-9.
  2. Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma. Khien VV, et al., Int J Biol Markers. 2001 Apr-Jun;16(2):105-11.
  3. Usefulness of measurement of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma. Hayashi K, et al., Am J Gastroenterol. 1999 Oct;94(10):3028-33.
  4. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Takata, K., et al., Cancer Res., 53, 5419–5423, 1993.
  5. Utility of lentil lectin affinity of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Wang, S., et al., J. Hepatology, 25, 166–171, 1996.
  6. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. Sato, Y., et al., N. Engl. J. Med., 328, 1802–1806, 1993.
  7. A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Shiraki, K., Hepatology, 22, 802–807, 1985.
  8. A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Shiraki, K., Hepatology, 22, 802–807, 1985.
  9. Prognostic significance of lens culinaris agglutinin A-reactive alpha-fetoprotein in small hepatocellular carcinoma. Yamashita, F., et al., Gastroenterology, 111, 996–1001, 1996.
  10. The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma. Aoyagi, Y., et al., Am. Cancer Soc., 83, 2076–2082, 1998.
  11. Monitoring of lectin-reactive alpha-fetoproteins in patients with hepatocellular carcinoma treated using transactheter arterial embolization. Yamashita, F., Eur. J. Gastroenterol. Hepatol., 7, 627–633, 1995.
  12. Evaluation of curability and prediction of prognosis after surgical for hepatocellular carcinoma by lens culinaris agglutinin-reactive alpha-fetoprotein. Okuda, K., et al., Inter. J. Oncol., 14, 265–271, 1999.
  13. Usefulness of lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) as a marker of distant metastasis from hepatocellular carcinoma. Yamashiki, N., et al., Oncology Reports, 6, 1229–1232, 1999.
  14. Relationship between lens culinaris agglutinin reactive alpha-fetoprotein and biological features of hepatocellular carcinoma. Kusaba, T., Kurume Med. J., 45, 113–120, 1998.
  15. Tumor vascularity and lens culinaris agglutinin reactive alpha-fetoprotein are predictors of long-term prognosis in patients with hepatocellular carcinoma after percutaneous ethanol injection therapy. Fukuda, H., Kurume Med. J., 45, 187–193, 1998.
  16. Clinical utility of lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: Special reference to imaging diagnosis. Kumada, T., et al., J. Hepatol., 30, 125–130, 1999.
  17. Deletion of serum lectin-reactive alpha-fetoprotein by Acyclic Retinoid: A potent biomarker in the chemoprevention of second primary hepatoma. Moriwaki, H., Clin. Cancer Res., 3, 727-731, 1997.
  18. Clinical utility of simultaneous measurement of serum high-sensitivity des-gamma-carboxy prothrombin and lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma. Sassa, T., et al., Eur. J. Gastroenterol. Hepatol. 11, 1387–1392, 1999.
  19. A simultaneous monitoring of lens culinaris agglutinin A-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients. Shimauchi, Y., et al., Oncology Reports, 7, 249–256, 2000.