Cytokeratin-7, cytokeratin-19, and c-Kit: Immunoreaction during the evolution stages of primary biliary cirrhosis

Aims: The quantitative and qualitative expression of CK-7, CK-19, and c-Kit markers in various cell types were evaluated during the four stages of primary biliary cirrhosis. Methods: A total of 53 specimens were examined. Thirteen specimens were identified as Ludwig's stage 1, 23 as stage 2, 14 as stage 3, and 2 as stage 4. Immunohistochemical stains were performed for CK-7, CK-19, c-Kit and subsequently graded. The cell types expressing the markers were qualitatively analysed. Results: In normal liver, biliary epithelial cells expressed CK-7, CK-19, whereas the Canals of Hering (CoH) were stained with c-Kit and partly CK-19, contrary to hepatocytes. The aforementioned expression patterns were detected in pathologic samples of PBC, with qualitative and quantitative differences though. CK-7 grading was found to correspond with Ludwig's staging, in contrast to CK-19. c-Kit was absent in the early stages and focally present in the advanced stages. All biliary-type, intermediate cells and hepatocytes were CK-7 positive, particularly in samples with cholestasis, whereas CK-19 was only found in biliary-type and intermediate cells. c-Kit was expressed in CoH which appeared as clusters and strings of cuboidal cells in advanced stages. Conclusions: CK-7 can be regarded as a histological marker of progression in PBC; CK-19 cannot be assessed as a safe marker in the development of the disease. The absence of c-Kit in the early stages of PBC is related to the destruction of the CoH. CK-7 hepatocyte expression in the advanced stages is likely to be related to damaged hepatocytes' metaplastic potential. (C) 2006 Elsevier Ireland Ltd. All rights reserved.