Expression of cytokeratin 7 as a histological marker of cholestasis and stages of primary biliary cirrhosis

Aušrinė Barakauskienė¹, Danutė Speičienė², Valentina Liakina², Teresė Semuchinienė², Jonas Valantinas²

¹National Center of Pathology, Vilnius University, ²Center of Hepatology, Gastroenterology, and Dietetics, Faculty of Medicine, Vilnius University, Lithuania

Key words: primary biliary cirrhosis; ductular reaction; cytokeratin 7; hepatitic/cholestatic pattern.

Summary. The aim of this study was to estimate cytokeratin 7 (CK-7) expression in biopsy specimens of patients with different stages of primary biliary cirrhosis and clinicopathological patterns (cholestatic and hepatitic) and its correlation with some biochemical and pathological parameters and to examine a diagnostic value of CK-7 expression.

Material and Methods. A total of 82 biopsy specimens of patients with primary biliary cirrhosis were analyzed. CK-7 expression was graded by 4 grades depending on the extent into parenchymal areas and bile duct epithelium. The correlations of CK-7 expression grade with copper deposition, bile duct/portal tract ratio, bilirubin concentration, and activity of alkaline phosphatase and gamma-glutamyl transpeptidase were studied. CK-7 expression was evaluated as a marker of cholestasis (cholestatic pattern) and inflammation (hepatitic pattern).

Results. A positive correlation of CK-7 expression grade with copper-binding protein grade (r=0.698, P<0.0001; OR=6.199, P<0.0001), serum bilirubin level (r=0.375, P=0.001), and alkaline phosphatase activity (r=0.276, p=0.014) was found. CK-7 expression grades correlated positively with histological stages of primary biliary cirrhosis (r=0.639, P<0.000) and negatively with granulomas (r=–0.432, P<0.0001; OR=0.173, P=0.0011).

Conclusions. CK-7 expression is a sensitive marker of bile duct injury, which correlated well with histological stages of primary biliary cirrhosis, copper deposits, and biochemical markers of cholestasis: serum bilirubin level and alkaline phosphatase activity. Evaluation of CK-7 expression may improve the diagnosis of this serious and progressive disease. It is recommended to evaluate copper staining together with cytokeratin 7 expression in liver biopsy specimens for more precise diagnostic evaluation of asymptomatic primary biliary cirrhosis.

Correspondence to V. Liakina, Center of Hepatology, Gastroenterology and Dietetics, Santariškių 2, 08661 Vilnius, Lithuania. E-mail: valentina.liakina@santa.lt

Received 28 November 2009, accepted 6 January 2011