METHODOLOGICAL ASPECTS

Alp ha-f etoprotein According to the definition recommended by WHO/IARC experts (World Health Organization and International Agency for Research on Cancer (Abelev et al. 1970)), AFP is the first alpha-globulin to appear in mammalian serum during development and the dominating serum protein in early embryonic life. It reappears in the adult serum during certain pathological states, primarily in hepatocellular carcinoma. Using paper electrophoresis, Bergstrand & Czar in 1956 first demonstrated AFP as an embryo-specific @-globulin in serum from the human fetus. In 1963 Abelev et al. showed that AFP is present not only in serum from fetal mice but also in adult mice carrying transplantable hepatomas. This fetal cyl-globulin was also detected in the blood of adult mice after partial hepatectomies but was not present in serum from mice carrying transplantable tumors other than hepatoma. Tatarinov (1964, 1965) observed a similar increase in the serum AFP concentration in patients with primary carcinoma of the liver. This observation was confirmed by Abelev et al. (1967) and Uriel et al. (1967), and simultaneously several groups (Abelev et al. 1967, Masopust et al. 1968) found that AFP was also present in serum from patients with malignant teratoblastoma of the testis and the ovary, possessing elements of embryonic character. In the very early human embryo, AFP is probably the dominant serum protein, being replaced later by albumin, which it resembles with respect to many physicochemical properties. In early embryogenesis AFP is produced first by the yolk sac and later by the liver (Gitlin & Boesman 1967, Gitlin & Perricelli 1970). A maximum concentration of AFP in fetal serum of about 3-4 g/l is found between the 12th and the 15th week of gestation, whereafter the concentration slowly declines. At birth the AFP concentration in cord serum from normal mature infants is 10-150 mg/l (van Furth & Adinolfi 1969, Nerrgaard-Pedersen 1972, 1973a, Seppala & Ruoslahti 1974). The serum AFP level in newborn babies falls rapidly within a few weeks to the adult level, which is so low that it is difficult to detect by gel precipitation methods (Gitlin & Boesman 1966, Norgaard-Pedersen 1973a). In normal healthy adults an AFP concentration of 1-16 pg/l can be measured by radioimmunoassays (Ruoslahti & Seppala 1972). Blood levels of AFP above 40 pg/l have been found in several malignant and benign diseases. In malignant diseases elevated blood AFP values are seen primarily in hepatomas and teratocarcinomas but also in a small percentage of some gastrointestinal malignancies (McIntire et al. 1974). Moderately elevated blood AFP values (25500 pg/l) have been found mainly in liver diseases associated with liver regeneration (Alpert & Coston 1975, Ruoslahti et al. 1974b), but increased amounts are also seen in serum from pztients with ataxia telangiectasia (Waldmann & McIntire 1972), in patients with tyrosinosis (BClanger et al. 1973a), in patients with cystic fibrosis (Chandra et al. 1975), and during pregnancy (Seppala & Ruoslahti 1972b). The biological function of human AFP is unknown. Rat AFP has a high affinity with estiogens, but human AFP does not have a similar binding activity (Savu et al. 1974). The protein was first purified and characterized chemically by Nishi (1970) and by Ruoslahti Seppala (1971a), and highly sensitive radioimmunoassay (RIA) methods for quantitation have been developed (Nishi & Hirai 1973, Ruoslahti & Seppala 1971b).