Des-gamma carboxyprothrombin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence or 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. Many hepatocellular carcinoma (HCC) cells however, lack the carboxylation activity and secrete unmodified prothrombin precursor DCP. DCP lacks thrombotic activity and many clinical research papers have shown that DCP is present in the sera of HCC patients [1-5].
In 1984, Liebman et al. found DCP in high prevalence with high specificity in sera of patients with HCC, and proposed it as a novel serum marker of HCC [6]. Many clinical studies have since shown that DCP is significantly elevated in HCC patients and that DCP was able to discriminate HCC from nonmalignant hepatopathy (i.e. chronic hepatitis B & hepatitis C and liver cirrhosis) with high specificity [2-5]. DCP level has also been demonstrated to be significantly associated with metastasis of tumor and the development of portal vein invasion (PVI) [7].
Though DCP has been used extensively in Japan for many years for HCC management, its clinical utility was only recently evaluated in the United States. Recent US studies reported that DCP is indeed effective in discriminating HCC from non-malignant hepatopathy for the North American demographic. A recently published case-controlled study reported that, DCP was able to differentiate early stage HCC from cirrhosis with high accuracy (at 150 mAU/mL): 92% sensitivity and 93% specificity. In addition, DCP identified 15 (88%) of 17 patients with early stage HCC that would have been missed utilizing the traditional HCC marker AFP alone during screening [4].
The target population to be screened for DCP is similar to that of another HCC marker, Lens culinaris reactive AFP (AFP-L3): patients with chronic hepatitis (CH), and cirrhosis. However, DCP is independently expressed. DCP therefore, is regarded as an independent and complimentary HCC marker for risk assessment, surveillance and detection of HCC [8-10].
References
1. Tsai et al. Plasma des-γ-carboxy prothrombin in the early stage of hepatocellular carcinoma. Hepatology 1990; 11(3):481-488.
2. Marrero, et al., Des-Gamma Carboxyprothrombin Can Differentiate Hepatocellular Carcinoma From Nonmalignant Chronic Liver Disease in American Patients. Hepatology 2003; 37:1114-1121
3. Cui R, et al., Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma. Chin Med J (Engl) 2002; 115(1):42-5.
4. Volk, M. et al., Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: A comparison of AFP, DCP, and AFP-L3. Cancer Biomarkers 2007; 3:79-87.
5. Liebman, H. A. et al., Des-γ-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. NEJM 1984; 310(22):1427-1431.
6. Lamerz R, et al., Use of serum PIVKA-II (DCP) determination for differentiation between benign and malignant liver disease. Anticancer Research. 1999; 19:2489-2494.
7. Koike, Y. et al., Des-γ-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma. Cancer 2001; 91:561-9.
8. Toyoda, H. et al., Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clinical Gastroenterology and Hepatology. 2006; 4:111-117.
9. Sterling R, et al., Clinical utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-γ-carboxy prothrombin (DCP) alone or in combination as biomarkers for hepatocellular carcinoma (HCC). Poster presentation at: Digestive Disease Week, May 19-23, 2007; Washington D.C.
10. Carr B, et al., Clinical Evaluation of Lens culinaris Agglutinin-Reactive α-Fetoprotein and Des-γ-Carboxy Prothrombin in Histologically Proven Hepatocellular Carcinoma in the United States. Dig Dis Sci. 2007; 52:776-782.