Evaluation of serum cytokeratin 19 as a tumor marker in patients with primary liver malignancy

ABSTRACT

The objective of this study was to evaluate the level of cytokeratin 19 related tumor marker CYFRA 21-1 in the sera of patients with chronic liver diseases [chronic viral hepatitis and liver cirrhosis] and primary hepatic malignancy and to find if it could be a significant tumor marker that can be used in the diagnosis of cholangiocarcinoma. The study was carried out on 69 patients attending Gastroenterology Centre, Mansoura University, in addition to 18 healthy controls. The selected subjects were divided into the following groups Group I included 18 patients with chronic viral C hepatitis. Group II included 17 patients with liver cirrhosis. Group Il included 14 patients with hepatocellular carcinoma Group IV included 20 patients with cholangiocarcinoma. Group IV included 20 patients with cholangiocarcinoma. Group V The control group and included 18 apparently healthy volunteers. Blood samples were collected from all patients as well as healthy volunteers, and the separated serum was divided into aliquots. One part was used immediately for the determination of liver function tests [serum albumin, total serum bilirubin, ALT, AST, and alkaline phosphatase]. The rest of the aliquots were stored frozen at -20 degree C until assayed for serum levels of Cytokeratin 19 fragment [CYFRA 21-1] and levels of a fetoprotein [AFP] by electro chemiluminescent immunoassay. The results of the present study showed that there was a statistically significant increase in CYFRA 21-1 level in CC group when compared with viral hepatitis [P<0.001], liver cirrhosis group [P-0.001] and with HCC group [P-<0.001], but there was no significant difference in CYFRA 21-1 level in HCC group when compared with viral hepatitis group, liver cirrhosis group. A significant positive correlation was found between CYFRA 21-1 and total bilirubin and AST in CC [P=0.006; [tau]b= 0.442 and [P=0.005; [tau]b=0.453]. At the same time, there was non-significant correlation between CYFRA 21-1 and AFP in all studied groups. In the present study, serum CYFRA 21-1 levels exceeded 4 ng/ml [double the upper limit of normal controls] in 11.1% of patients with viral hepatitis, 29.4% of patients with liver cirrhosis, 21.4% of patients with HCC and 60% of patients with CC. To compare the ability of both AFP and CYFRA 21-1 in differentiating primary malignant liver tumors, we have performed Receiver operator characteristic [ROC] curves. From the data of ROC curve we can found that CYFRA 21-1 is superior to AFP in the diagnosis of CC from other primary liver malignancy as HCC. On the other hand, AFP was superior in differentiating HCC from CC. From the present study, we can conclude that the measurement of serum levels of CYFRA 21-1 can be utilized in the differential diagnosis of cholangiocarcinoma from other primary liver malignancies. So, we recommend the measurement of serum level of CYFRA 21-1 in all patients with hepatic mass to differentiate between hepatocellular carcinoma and cholangiocarcinoma, particularly the liver biopsy is not preferred. When the serum levels of CYFRA 21-1 increase in some patients with benign liver diseases, particularly liver cirrhosis on top of chronic viral hepatitis C infection, this may attract attention towards the possibility of malignant transformation