Expression of Cytokeratin 7 as a Histological Marker of Cholestasis and Stages of Primary Biliary Cirrhosis

Aušrinė Barakauskienė,Teresė Semuchinienė,Valentina Liakina,Danutė Speičienė,Jonas Valantinas

doi:10.3390/medicina47010005

Aušrinė Barakauskienė, Teresė Semuchinienė + Show 3 more

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https://doi.org/10.3390/medicina47010005

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Journal: Medicina	Publication Date: Jan 11, 2011
Citations: 7	License type: CC BY 4.0

Affiliation: Vilnius University

Abstract

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. 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). 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). 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.

Highlights

The term “ductular reaction” introduced by Popper in 1957 refers to an increased number of periportal ductular structures consisting of either proliferation of preexisting ductules or activation of progenitor cells and intermediate hepatocytes [1,2,3,4,5]
cytokeratin 7 (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
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

Summary

Introduction

The term “ductular reaction” introduced by Popper in 1957 refers to an increased number of periportal ductular structures consisting of either proliferation of preexisting ductules or activation of progenitor cells and intermediate hepatocytes [1,2,3,4,5]. Bile ductular reactions occur in a variety of human liver diseases [6,7,8,9,10,11,12,13,14,15,16,17]. Bile duct injury resembling that observed in primary biliary cirrhosis (PBC) to variable degree can be encountered in other diseases [15]. For this reason, special staining techniques that highlight specific antigens and structures are very useful for better visualization of ductular reaction [11, 14, 16, 17, 20,21,22,23]

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