Des-y-carboxy (abnormal) prothrombin (DCP) is a newly described tumor marker for HCC (I). In 1984, Liebman et al. found DCP in the plasma of nearly 90% of patients with HCC, suggesting that this protein could be utilized as a tumor marker for this malignancy. Since the initial report, this observation has been confirmed by several investigators using a variety of assay systems (2-13). The mechanism(s1 responsible for the secretion of DCP into the blood of patients with primary liver cancer remains a matter of speculation. However, the malignant hepatocyte appears to be directly responsible for the production of this protein; resection of this tumor results in decreased blood levels of this protein (1,6,12). In this article, current knowledge of DCP secretion and its use in monitoring patients with HCC will be reviewed.
VITAMIN K-DEPENDENT CARBOXYLATION OF
BLOOD CLOTTING PROTEINS Twenty-nine plasma proteins involved in hemostatic regulation have been functionally and structurally characterized (14). Most are synthesized in the liver. Six of these proteins, four procoagulant (factors VII, IX and X and prothrombin) and two anticoagulant (proteins C and S), require vitamin K for their complete biosynthesis (14).
Vitamin K is required for modification of the aminoterminal portions of prothrombin and other vitamin K-dependent coagulation proteins, which are essential for calcium binding (15, 16) (Fig. 1). In 1974, Stenflo et al. (17) and Nelsestuen et al. (18) independently demonstrated that the amino-terminal domain of prothrombin contained a unique calcium ion (Ca++)binding amino acid, y-carboxyglutamic acid (GLA). Prothrombin deficient in GLA, DCP, cannot bind Ca' + and therefore lacks functional activity. GLA is synthe-