DCP Flyer deutsch Wako chemicals - Wako Chemicals GmbH

The interpretation of positive AFP and DCP results is different. Although
both markers are described to correlate with disease progression
and tumor diameter [7], DCP has been shown to be an improved
marker of further biological characteristics of HCC. Koike et al.
reported that DCP was the most significant predisposing factor for
the development of portal vein invasion (PVI), an indicator of advanced
HCC [8]. HCC patients with elevated DCP but normal AFP tend
to have more advanced HCC as shown by Okuda et al. [9].
DCP measurements are very useful during the follow-up after the
first treatment of tumors. As a significant prognostic factor DCP is effective
in predicting HCC recurrence. Kaibori et al. analysed 29 clinicopathologic
factors in 143 patients with recurrent HCC and concluded
that the monitoring of both tumor markers AFP and DCP is
essential for improving the prognosis after recurrence [10].
MEASUREMENT OF DCP
The measurement of DCP is carried out fully-automated by the
LiBASys TM
- (Liquid-phase Binding Assay System) instrument of the
company Wako Chemicals GmbH (Fig. 3). This instrument can also
measure AFP-L3% together
with (total) AFP.
In each measurement
the markers are determined
using a liquidphase
binding assay
with subequent fractionation
of the markers
and unbound
analyte-specific by ionexchange
column chromatography
[11]. This
Fig. 3: LiBASys
system enables any laboratory to complement the panel of the
currently mostly validated HCC biomarkers.
TM instrument
REFERENCES
[1] Michielsen PP, Francque SM, van Dongen JL: Viral hepatitis and hepatocellular
carcinoma. World J Surg Oncol 2005, 3:27
[2] Bruix J, Sherman M, Llovet JM et al.: Clinical management of hepatocellular
carcinoma: conclusions of the Barcelona 2000 EASL conference. European
Association for the Study of the Liver. J Hepatol 2001, 35: 421-430
[3] Tang W et al.: Des-gamma-carboxy prothrombin in cancer and non-cancer liver
tissue of patients with hepatocellular carcinoma. Int J Oncol 2003, 22: 969-975
[4] Liebman HA et al.: Des-gamma-carboxy (abnormal) prothrombin as a serum marker
of primary hepatocellular carcinoma. N Engl J Med 1984, 310: 1427-1431
[5] Spangenberg HC, Thimme R, Blum HE: Serum Markers for Hepatocellular
Carcinoma. Semin Liver Dis 2006, 26: 385-390
[6] Kanke F et al.: Clinical utility of Lens culinaris agglutinin-reactive fraction of alphafetoprotein
(AFP-L3%) and des- -carboxy prothrombin (DCP) alone or in
combination as biomarker for hepatocellular carcinoma (HCC). Poster accepted at
AACC congress, San Diego, USA, 2007
[7] Nakamura S 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, 101: 2038-2043
[8] Koike Y et al.: Des-gamma carboxy prothrombin as a useful predisposing factor for
the development of portal venous invasion in patients with hepatocellular carcinoma.
Cancer 2001, 91: 561-569
[9] Okuda H 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, 6: 1290-1296
[10] Kaibori M et al.: Positive status of alpha-fetoprotein and des-gamma-carboxy
prothrombin: important prognostic factor for recurrent hepatocellular carcinoma.
World J Surg 2004, 28(7):702-707
[11] Yamagata Y et al.: Simultaneous determination of percentage of Lens culinaris
agglutinin-reactive -fetoprotein and -fetoprotein concentration using the LiBASys
clinical auto-analyzer. Clin Chim Acta 2003, 327: 59-67
For any questions please contact Dr. Robert Kueper, Tel.: +49 (0)2131 2099354,
e-mail: robert.kueper@wako-chem-co.de
Rev. 1007 GB
Fuggerstraße 12 • D-41468 Neuss • Germany
Telephone +49 (2131) 311-0
Facsimile +49 (2131) 311-100
e-mail: diagnostika@wako-chemicals.de
www.wako-chemicals.de
DCP
HCC
Diagnostics
Significance
DCP

HEPATOCELLULAR CARCINOMA
Hepatocellular Carcinoma (HCC) ranks globally among one of the five
most common carcinomas of males. It is the most important type of liver
cancer, because it represents at least 80% of the primary malignant liver
tumors in adults. Europe is regarded to be a geographic area of low incidence
in Northern and Western parts and medium incidence in Southern
and Eastern regions, where age-adjusted incidence rates of about 10
per 100.000 in men are reported [1].
Most studies show an alarming increase of the mortality rate of to HCC
in the recent years. Presently in Europe about 30.000 persons are dying
annually due to HCC. The most important risk factors for the development
of HCC are chronic liver diseases caused by viral hepatitis B and C
and alcohol abuse, while the significance of each individual factor differs
from country to country. Haemochromatosis, primary biliary cirrhosis and
autoimmune hepatitis also increase the risk of HCC development.
SCREENING AND DIAGNOSTICS
Unfortunately the diagnosis of HCC mostly occurs in advanced stages
of cancer, so that curative treatments are mostly not possible. In Europe
more than 80 % of HCC cases develop on the background of a cirrhotic
liver. Cirrhotic patients are therefore regarded to be patients of
high risk. In practice they undergo surveillance programs with abdominal
ultrasound investigations and determinations of -fetoprotein (AFP)
twice per year. The rationale for surveillance is to detect HCC at an early
stage to allow curative treatments. After detection of suspicious lesions
during surveillance more sophisticated imaging techniques are
available to diagnose HCC.
The serum marker AFP is the only routinely used HCC marker, but its
clinical significance is limited. Both the sensitivity and the specificity
are low [2]. Particularly in the „grey zone“ between 10 and 200 ng/ml
AFP many investigated patients don’t have a HCC, so that the decision
to use further diagnostic options is difficult. Furthermore about one
third of HCC patients don’t show diagnostic relevant elevations of the
AFP concentration. A generally accepted diagnostic cut-off for this tumor
marker doesn’t exist.
WHAT IS DCP?
Des-gamma-carboxy prothrombin (DCP) is an immature form of the
coagulation protein, prothrombin. In the normal metabolism the
prothrombin precursor undergoes a vitamin K dependent carboxylation
of 10 glutamic-acid residues at the N-terminus to yield the native
prothrombin. In the case of HCC this transformation is impaired by abnormalities
in prothrombin precursors, reduced carboxylase activity,
shortage or increased demand of vitamin K [3], which results in an accumulation
of DCP (Fig 1). DCP is also known as protein induced by
vitamin K absence or antagonist II (PIVKA-II).
Fig. 1: Schematic figure of DCP accumulation during HCC
In 1984, Liebman et al. reported for the first time that DCP is a promising
biomarker for HCC [4]. In Japan DCP has been routinely used for
many years as tumor marker for HCC. Since early 2007 DCP is FDA
approved in the USA for the risk assessment of HCC. Since mid of
2007 this product is also CE-marked for the European market.
DCP
CLINICAL SIGNIFICANCE OF DCP
DCP is elevated in up to 60% of HCC patients. In many reports sens-
itivities between 28 und 89% and specificities between 87% and
96% were reported [5].
Recently a multicenter, prospective study has been performed in the
USA and Canada. Out of 372 investigated patients 40 had HCV-related
HCC at entry and 332 patients with HCV related cirrhosis were
followed up for up to 2 years. Of the latter group 34 patients developed
HCC. As can be seen in table 1 in this study DCP showed a
much higher specificity and positive predictive value than AFP for
the detection of HCC [6].
Table 1: Diagnostic parameters of DCP versus AFP
AFP DCP
Cut-off 20 ng/ml 7,5 ng/ml
Sensitivity 61 % 39 %
Specificity 71 % 90 %
Positive predictive value 34 % 48 %
Negative predictive vaule 88 % 86 %
It is well known that there is no correlation between AFP and DCP.
The combination of both tests is therefore reasonable to improve the
accuracy of HCC diagnostics. In the above mentioned study an increased
overall sensitivity could be demonstrated (Fig. 2).
DCP>7,5 ng/ml
7 (9,5%)
All negative 22 (29,7%)
22 (29,7%)
AFP>20 ng/ml
23 (31,1%)
Fig. 2: Positive patient number of DCP and AFP in patients with HCC (n=74)