Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis

Yabushita, Kazuhisa; Yamamoto, Kazuhide; Ibuki, Naohisa; Okano, Nobuaki; Matsumura, Shuji; Okamoto, Ryoichi; Shimada, Noriaki; Tsuji, Takao

doi:10.1034/j.1600-0676.2001.210108.x

Cited by 46 publications

(44 citation statements)

References 17 publications

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“…In primary biliary cirrhosis aberrant expression of CK7 by hepatocytes correlates with the degree of cholestasis. 27 These results suggest that CK7 expression in hepatocellular carcinoma did not merely reflect the origin of tumor cells.…”

Section: Ezrin and Hepatocellular Carcinoma D Okamura Et Almentioning

confidence: 90%

Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection

et al. 2008

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Heterogeneous biological characteristics of hepatocellular carcinoma may be attributed to the cellular origin of the tumor. Patients with hepatocellular carcinoma probably derived from hepatic progenitor cells had early tumor recurrence after surgical resection or liver transplantation, suggesting that these tumors have aggressive characteristics. Ezrin, a member of the ERM (ezrin-radixin-moesin) cytoskeleton-associated protein family, is highly expressed in several types of human cancers and correlations between its immunoreactivity and patient outcome have been shown. In this study, ezrin expression, as well as cytokeratin19 and cytokeratin 7 expression, which are regarded as progenitor cell/ductular markers were immunohistochemically assessed in cases of hepatocellular carcinoma. In normal livers, ezrin expression was not found in any cell types, whereas cytokeratin 7 and cytokeratin 19 were exclusively stained in bile duct cells. In contrast, in livers with chronic hepatitis or cirrhosis, positive ezrin expression was observed in ductular reactions with strong intensity and intermediate hepatobiliary cells with various intensity. Of 77 cases of hepatocellular carcinoma, 28 (36%) had positive ezrin expression, 32 (42%) had cytokeratin 7 expression, and 11 (14%) had cytokeratin 19 expression. Ezrin expression in hepatocellular carcinoma was significantly associated with cytokeratin 19 expression, but not with cytokeratin 7 expression. Patients with ezrin-positive hepatocellular carcinoma had a significantly higher prevalence of elevated serum a-fetoprotein. Patients with immunohistochemical ezrin-positive hepatocellular carcinoma demonstrated significantly shorter recurrence-free and overall survival compared to patients with ezrin-negative hepatocellular carcinoma. Multivariate analysis revealed positive ezrin expression and multiple tumors to be independently associated with early recurrence in patients with hepatocellular carcinoma after curative surgical resection. These results suggested that hepatocellular carcinoma with ezrin expression might be at least partly derived from hepatic progenitor cells. Measurement of ezrin expression might be used to identify patients with an increased risk of early recurrence.

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Section: Ezrin and Hepatocellular Carcinoma D Okamura Et Almentioning

confidence: 90%

Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection

et al. 2008

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“…Five-micrometer sections were prepared from paraffin-embedded samples and used for immunohistochemical staining of SDF-1, as described previously (Yabushita et al, 2001). Briefly, sections were pretreated at 100°C in a microwave oven in 0.1 M sodium citrate solution for 10 minutes and incubated with mAb for SDF-1 (R&D Systems, Minneapolis, Minnesota) overnight at 4°C after nonspecific binding was blocked with 10% goat serum (Nichirei, Tokyo, Japan).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

Terada

Yamamoto

Hakoda

et al. 2003

Laboratory Investigation

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SUMMARY:Although stromal cell-derived factor-1 (SDF-1) plays an important role in hematopoiesis in the fetal liver, the role after birth remains to be clarified. We investigated the role of SDF-1 and its receptor, CXCR4, in 75 patients; this included controls and patients with viral hepatitis, liver cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Interestingly, SDF-1 appeared up-regulated in biliary epithelial cells (BEC) of inflammatory liver disease. Furthermore, in inflammatory liver diseases, SDF-1 was expressed by BEC of interlobular and septal bile ducts and by proliferated bile ductules. The message expression of SDF-1 in BEC was confirmed at a single-cell level by RT-PCR and laser capture microdissection. The plasma levels of SDF-1 were significantly higher in patients with liver diseases than in normal controls. Flow cytometric analysis of the surface expression of CXCR4 showed that most liver-infiltrating lymphocytes express CXCR4 and the intensity was up-regulated more significantly in liver-infiltrating lymphocytes than in peripheral blood lymphocytes. These results suggest that increased SDF-1 production by BEC may play an important role in the recruitment of CXCR4-positive inflammatory cells into the diseased livers. These data are significant because modulation of the SDF-1/CXCR4 interaction has therapeutic implications for inflammatory liver diseases. (Lab Invest 2003, 83:665-672).

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“…[6][7][8] Expression of CK7 in these conditions is though to represent a metaplastic phenomenon in which these cells take on a hybrid phenotype between a hepatocyte and cholangiocyte. Thus, it was quite surprising that CK7 was expressed in perivenular hepatocytes in the majority of patients with heart failure in this study.…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a cholestatic chemistry profile in patients with heart failure

Pai

Hart

2010

Modern Pathology

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A cholestatic liver chemistry profile (elevations in alkaline phosphatase and bilirubin) is commonly encountered in patients with hepatic venous outflow obstruction due to right heart failure. Liver biopsies from these patients demonstrate varying degrees of sinusoidal dilatation, red blood cell extravasation and sinusoidal congestion. Recently, a bile ductular reaction mimicking biliary tract disease has been identified in B50% of patients with venous outflow obstruction possibly explaining the cholestatic profile encountered in these patients. In this study, we evaluated the liver biopsies from 22 patients with heart failure. Marked sinusoidal dilatation involving zones 2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22 patients had histologic evidence of a mild ductular reaction. Cytokeratin 7 immunohistochemistry revealed a mild ductular reaction in an additional two cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20 of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however, in five cases it was quite extensive and extended into zone 2. There was no significant association between marked sinusoidal dilatation and extensive perivenular CK7 positivity. Extensive perivenular CK7 positivity was significantly associated with both elevated bilirubin, as well as the presence of fibrosis. However, a ductular reaction was not associated with a cholestatic liver chemistry profile.

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Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis

Abstract: These results suggest that the aberrant expression of CK-7 in hepatocytes may be a marker of chronic cholestasis and progression in PBC.

Cited by 46 publications

References 17 publications

Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection

Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a cholestatic chemistry profile in patients with heart failure

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