Oncofetal Antigens

Oncofetal antigens are proteins that are expressed at high levels in cancer cells and in normal developing fetal but not adult tissues. It is believed that the genes encoding these proteins are silenced during development and are derepressed with malignant transformation. Oncofetal antigens are identified with antibodies raised in other species, and their main importance is that they provide markers that aid in tumor diagnosis. As techniques for detecting these antigens have improved, it has become clear that their expression in adults is not limited to tumors. The proteins are increased in tissues and in the circulation in various inflammatory conditions and are found in small quantities even in normal tissues. There is no evidence that oncofetal antigens are important inducers or targets of anti-tumor immunity. The two most thoroughly characterized oncofetal antigens are carcinoembryonic antigen (CEA) and a-fetoprotein (AFP).

CEA (CD66) is a highly glycosylated membrane protein that is a member of the immunoglobulin (Ig) superfamily and functions as an intercellular adhesion molecule. High CEA expression is normally restricted to cells in the gut, pancreas, and liver during the first two trimesters of gestation, and low expression is seen in normal adult colonic mucosa and the lactating breast. CEA expression is increased in many carcinomas of the colon, pancreas, stomach, and breast, and serum levels are increased in these patients. The level of serum CEA is used to monitor the persistence or recurrence of the tumors after treatment. The usefulness of CEA as a diagnostic marker for cancer is limited by the fact that serum CEA can also be elevated in the setting of non-neoplastic diseases, such as chronic inflammatory conditions of the bowel or liver.

AFP is a circulating glycoprotein normally synthesized and secreted in fetal life by the yolk sac and liver. Fetal serum concentrations can be as high as 2 to 3 mg/mL, but in adult life, the protein is replaced by albumin, and only low levels are present in serum. Serum levels of AFP can be significantly elevated in patients with hepato-cellular carcinoma, germ cell tumors, and, occasionally, gastric and pancreatic cancers. An elevated serum AFP level is a useful indicator of advanced liver or germ cell tumors or of recurrence of these tumors after treatment. Furthermore, the detection of AFP in tissue sections by immunohistochemical techniques can help in the pathologic identification of tumor cells. The diagnostic value of AFP as a tumor marker is limited by the fact that elevated serum levels are also found in non-neoplastic diseases, such as cirrhosis of the liver.

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