Des-?-carboxy Prothrombin (DCP)

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Category:

Turnaround Time: 5 - 7 days
CPT Code:

83951

Test Type: 0.5 mL Serum, frozen
Reference Range:

0.0-7.5 ng/mL

Overview:

DCP is intended for use as an aid in the risk assessment of patients with chronic liver disease for progression to hepatocellular carcinoma in conjunction with other laboratory findings, imaging studies, and clinical assessment.1

It is recommended that this assay be used in conjunction with imaging studies for clinical diagnosis.

Hepatocellular carcinoma (HCC) is a highly fatal cancer that results in approximately 10,000 deaths in the United States each year.2,3 The objective of the HCC screening programs is to find small lesions when potential curative treatment options are available.3,4 The tests commonly employed for screening are imaging of the liver by ultrasound and measurement of serum α-fetoprotein (AFP) levels.2,5 This arsenal has recently been enhanced through the addition of the AFP-L3% test.6

Des-γ-carboxy prothrombin (DCP), also referred to as protein induced by vitamin K absence (PIVKA-II), is a nonfunctional precursor of prothrombin.7 Prothrombin, produced by the liver, serves a critical role in normal hemostasis. Functional prothrombin contains several γ-carboxy-glutamic acid (Gla) residues that are produced as result of post-translational modification of glutamic acid residues mediated by vitamin K-dependent γ-glutamyl carboxylase. The formation of Gla residues can be impaired in patients with vitamin K deficiency or in patients receiving oral anticoagulant therapy. DCP lacks thrombotic activity and has been shown in multiple studies to be present in the serum of patients with HCC.7-13

Patients who test positive for DCP often exhibit clinical features of HCC that are different from those who test postive for AFP-L3.9-15 Published studies have indicated that DCP elevation reflects the progression of the disease and tumor diameter.9-15 Increased DCP levels have been associated with the development of portal vein invasion (PVI), a strongly negative prognostic indicator.9 Patients with elevated DCP and normal AFP tend to have more advanced HCC.10-14 Volk and coworkers showed that DCP can be particularly useful in the assessment of HCC risk in high-risk patients.16

The combined use of the three biomarkers, AFP, AFP-L3%, and DCP can support the discrimination between benign and malignant conditions related to primary liver disease.10,11,14,15 DCP and AFP-L3% are considered complementary assays for assessing the risk of developing HCC.1 When used in combination, a greater number of patients at risk of developing HCC can be identified resulting in more treatment options for a larger number of patients.1

DCP/PIVKA-II has also been used for the assessment of the vitamin K status of newborns.17 Vitamin K deficiency may cause unexpected bleeding during the first week of life in previously healthy-appearing neonates.17,18 This condition has been referred to as early vitamin K deficiency bleeding (VKDB) of the newborn or classic hemorrhagic disease of the newborn. Vitamin K prophylaxis (oral or parenteral) has been found to be effective in the prevention of this condition.18 Late VKDB, defined as unexpected bleeding attributable to severe vitamin K deficiency in infants 2 to 12 weeks of age, can occur in exclusively breast-fed infants who have received inadequate neonatal vitamin K prophylaxis.17,18 Infants with intestinal malabsorption defects (cholestatic jaundice, cystic fibrosis, etc) may also have late VKDB.17,18

1. LBA DCP Manufacturer’s package insert, Code No. 993-05301, Wako Pure Chemical Industries.

2. Johnson PJ. Tumor markers in primary malignancies of the liver. In: Diamandis EP, Fritshce HA, Lilja H, et al, eds. Tumor Markers: Physiology, Pathobiology, Technology and Clinical Applications. Washington, DC: AACC Press; 2002: 269-279.

3. El-Serag HB. Hepatocellular carcinoma: Recent trends in the United States. Gastroenterol. 2004 Nov; 127(5 Suppl 1):S27-S34. PubMed 15508094

4. Sherman M, Takayama Y. Screening and treatment for hepatocellular carcinoma. Gastroenterol Clin North Am. 2004 Sep; 33(3):671-691, xi. PubMed 15324950

5. Di Bisceglie AM. Issues in screening and surveillance for hepatocellular carcinoma. Gastroenterol. 2004 Nov; 127(5 Suppl 1):S104-S107. PubMed 15508072

6. Leerapun A, Suravarapu SV, Bida JP, et al. The utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: Evaluation in a United States referral population. Clin Gastroenterol Hepatol. 2007 Mar; 5(3):394-402. PubMed 17368240

7. Lamerz R, Runge M, Stieber P, Meissner E. Use of serum PIVKA (DCP) determination for differentiation between benign and malignant liver diseases. Anticancer Res. 1999 Jul-Aug; 19(4A):2489-2493. PubMed 10470180

8. Sterling RK, Jeffers L, Gordon F, et al. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. Am J Gastroenterol. 2007 Oct; 102(10):2196-2205. PubMed 17617202

9. Koike Y, Shiratori Y, Sato S, et al. Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: A prospective analysis of 227 patients. Cancer. 2001 Feb 1; 91(3):561-569. PubMed 11169939

10. Okuda H, Nakanishi T, Takatsu K, et al. Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and those seropositive for des-gamma-carboxy prothrombin alone. J Gastroenterol Hepatol. 2001 Nov; 16(11):1290-1296. PubMed 11903749

11. Kaibori M, Matsui Y, Yanagida H, Yokoigawa N, Kwon AH, Kamiyama Y. Positive status of alpha-fetoprotein and des-gamma-carboxy prothrombin: Important prognostic factor for recurrent hepatocellular carcinoma. World J Surg. 2004 Jul; 28(7):702-707. PubMed 15185000

12. Wang CS, Lin CL, Lee HC, et al. Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma. World J Gastroenterol. 2005 Oct 21; 11(39):6115-6119. PubMed 16273636

13. Nakamura S, Nouso K, Sakaguchi K, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinoma varies according to tumor size. Am J Gastroenterol. 2006 Sep; 101(9):2038-2043. PubMed 16848811

14. Toyoda H, Kumada T, Kiriyama S, et al. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006 Jan; 4(1):111-117. PubMed 16431313

15. Carr BI, Kanke F, Wise M, Satomura S. Clinical evaluation of Lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci. 2007 Mar; 52(3):776-782. PubMed 17253135

16. Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: A comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 2007; 3(2):79-87. PubMed 17522429

17. von Kries R, Greer FR, Suttie JW. Assessment of vitamin K status of the newborn infant. J Pediatr Gastroenterol Nutr. 1993 Apr; 16(3):231-238. PubMed 8492247

18. American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. Pediatrics., 2003 Jul; 112(1 Pt 1):191-192. PubMed 12837888

Collection Details:

Collection Instructions:

Red-top tube or gel-barrier tube.

Separate serum from cells and transfer to a plastic transport tube. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.

Freeze.