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Immunohistochemical detection of polyductin and co-localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas.

Dorn L, Menezes LF, Mikuz G, Otto HF, Onuchic LF, Sergi C - J. Cell. Mol. Med. (2008)

Bottom Line: No specific staining was found at the stage of remodelled bile ducts.Polyductin was also co-localized in some DP cells together with oval stem cell markers.These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree, and support the following conclusions: (i) polyductin expression mirrors developmental properties of the primitive intrahepatic biliary system; (ii) polyductin is re-expressed in pathological conditions associated with DPM and (iii) polyductin might be a potential marker to distinguish CCC from HCC.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University of Innsbruck, Innsbruck, Austria.

ABSTRACT
The longest open reading frame of PKHD1 (polycystic kidney and hepatic disease 1), the autosomal recessive polycystic kidney disease (ARPKD) gene, encodes a single-pass, integral membrane protein named polyductin or fibrocystin. A fusion protein comprising its intracellular C-terminus, FP2, was previously used to raise a polyclonal antiserum shown to detect polyductin in several human tissues, including liver. In the current study, we aimed to investigate by immunohistochemistry the detailed polyductin localization pattern in normal (ductal plate [DP], remodelling ductal plate [RDP], remodelled bile ducts) and abnormal development of the primitive intrahepatic biliary system, known as ductal plate malformation (DPM). This work also included the characterization of polyductin expression profile in various histological forms of neonatal and infantile cholestasis, and in cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC). We detected polyductin expression in the intrahepatic biliary system during the DP and the RDP stages as well as in DPM. No specific staining was found at the stage of remodelled bile ducts. Polyductin was also detected in liver biopsies with neonatal cholestasis, including mainly biliary atresia and neonatal hepatitis with ductular reaction as well as congenital hepatic fibrosis. In addition, polyductin was present in CCC, whereas it was absent in HCC. Polyductin was also co-localized in some DP cells together with oval stem cell markers. These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree, and support the following conclusions: (i) polyductin expression mirrors developmental properties of the primitive intrahepatic biliary system; (ii) polyductin is re-expressed in pathological conditions associated with DPM and (iii) polyductin might be a potential marker to distinguish CCC from HCC.

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Polyductin expression and co-staining. (A) Microphotograph of the liver specimen with Caroli’s disease (stage: cirrhosis) showing a moderate to intense Ep-CAM staining of the biliary epithelium and focal co-staining with FP2 (arrow) at the limiting plate of the portal tract (anti-FP2 brown, anti-Ep-CAM red, ×400; the biliary structure indicated by the arrow is also shown in the inset); in (B) is shown a portal tract from a liver specimen with chronic rejection and paucity of the interlobular bile ducts (bile duct to portal tract ratio: 0.3) showing a portal tract with a residual bile duct and CK-19 staining of the bile duct epithelium and more co-staining at the limiting plate and in some biliary structures (orange staining, arrow) (anti-FP2 brown, anti-CK19 red, ×400). The segmented arrow shows a biliary duct with co-staining (also shown in the inset); in (C) co-CK19 and FP2 staining (arrow) is shown in the limiting plate of this portal tract from a liver specimen with acute rejection (anti-FP2 brown, anti-CK19 red, ×400; in the inset is the biliary structure shown by the arrow); in (D) is also shown the portal tract of a liver specimen with acute rejection showing some FP2 staining (brown) and co-staining of ductal plate cells (arrow with solid line) and biliary structures with MUC-1 (arrows with segmented lines, also demonstrated in the inset) (anti-FP2 brown, anti-MUC-1 red, ×400).
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fig05: Polyductin expression and co-staining. (A) Microphotograph of the liver specimen with Caroli’s disease (stage: cirrhosis) showing a moderate to intense Ep-CAM staining of the biliary epithelium and focal co-staining with FP2 (arrow) at the limiting plate of the portal tract (anti-FP2 brown, anti-Ep-CAM red, ×400; the biliary structure indicated by the arrow is also shown in the inset); in (B) is shown a portal tract from a liver specimen with chronic rejection and paucity of the interlobular bile ducts (bile duct to portal tract ratio: 0.3) showing a portal tract with a residual bile duct and CK-19 staining of the bile duct epithelium and more co-staining at the limiting plate and in some biliary structures (orange staining, arrow) (anti-FP2 brown, anti-CK19 red, ×400). The segmented arrow shows a biliary duct with co-staining (also shown in the inset); in (C) co-CK19 and FP2 staining (arrow) is shown in the limiting plate of this portal tract from a liver specimen with acute rejection (anti-FP2 brown, anti-CK19 red, ×400; in the inset is the biliary structure shown by the arrow); in (D) is also shown the portal tract of a liver specimen with acute rejection showing some FP2 staining (brown) and co-staining of ductal plate cells (arrow with solid line) and biliary structures with MUC-1 (arrows with segmented lines, also demonstrated in the inset) (anti-FP2 brown, anti-MUC-1 red, ×400).

Mentions: We have also performed double staining analyses in additional liver biopsies (Fig. 5A–D). A liver sample with Caroli’s disease, at a cirrhotic stage, showed moderate to intense Ep-CAM staining of the biliary epithelium and focal co-staining with FP2 at the limiting plate of the portal tract (Fig. 5A). A liver sample with chronic rejection with paucity of the interlobular bile ducts, in turn, revealed CK-19 staining of the bile duct epithelium and co-staining with FP2 at the limiting plate and in some biliary structures (Fig. 5B). The post-transplantation liver sample showing features of acute rejection revealed co-staining of CK19 and FP2 at the limiting plate of the portal tracts (Fig. 5C). In the same liver specimen, we could also detect FP2-staining with co-staining of the biliary structures with MUC-1 (Fig. 5D).


Immunohistochemical detection of polyductin and co-localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas.

Dorn L, Menezes LF, Mikuz G, Otto HF, Onuchic LF, Sergi C - J. Cell. Mol. Med. (2008)

Polyductin expression and co-staining. (A) Microphotograph of the liver specimen with Caroli’s disease (stage: cirrhosis) showing a moderate to intense Ep-CAM staining of the biliary epithelium and focal co-staining with FP2 (arrow) at the limiting plate of the portal tract (anti-FP2 brown, anti-Ep-CAM red, ×400; the biliary structure indicated by the arrow is also shown in the inset); in (B) is shown a portal tract from a liver specimen with chronic rejection and paucity of the interlobular bile ducts (bile duct to portal tract ratio: 0.3) showing a portal tract with a residual bile duct and CK-19 staining of the bile duct epithelium and more co-staining at the limiting plate and in some biliary structures (orange staining, arrow) (anti-FP2 brown, anti-CK19 red, ×400). The segmented arrow shows a biliary duct with co-staining (also shown in the inset); in (C) co-CK19 and FP2 staining (arrow) is shown in the limiting plate of this portal tract from a liver specimen with acute rejection (anti-FP2 brown, anti-CK19 red, ×400; in the inset is the biliary structure shown by the arrow); in (D) is also shown the portal tract of a liver specimen with acute rejection showing some FP2 staining (brown) and co-staining of ductal plate cells (arrow with solid line) and biliary structures with MUC-1 (arrows with segmented lines, also demonstrated in the inset) (anti-FP2 brown, anti-MUC-1 red, ×400).
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Related In: Results  -  Collection

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fig05: Polyductin expression and co-staining. (A) Microphotograph of the liver specimen with Caroli’s disease (stage: cirrhosis) showing a moderate to intense Ep-CAM staining of the biliary epithelium and focal co-staining with FP2 (arrow) at the limiting plate of the portal tract (anti-FP2 brown, anti-Ep-CAM red, ×400; the biliary structure indicated by the arrow is also shown in the inset); in (B) is shown a portal tract from a liver specimen with chronic rejection and paucity of the interlobular bile ducts (bile duct to portal tract ratio: 0.3) showing a portal tract with a residual bile duct and CK-19 staining of the bile duct epithelium and more co-staining at the limiting plate and in some biliary structures (orange staining, arrow) (anti-FP2 brown, anti-CK19 red, ×400). The segmented arrow shows a biliary duct with co-staining (also shown in the inset); in (C) co-CK19 and FP2 staining (arrow) is shown in the limiting plate of this portal tract from a liver specimen with acute rejection (anti-FP2 brown, anti-CK19 red, ×400; in the inset is the biliary structure shown by the arrow); in (D) is also shown the portal tract of a liver specimen with acute rejection showing some FP2 staining (brown) and co-staining of ductal plate cells (arrow with solid line) and biliary structures with MUC-1 (arrows with segmented lines, also demonstrated in the inset) (anti-FP2 brown, anti-MUC-1 red, ×400).
Mentions: We have also performed double staining analyses in additional liver biopsies (Fig. 5A–D). A liver sample with Caroli’s disease, at a cirrhotic stage, showed moderate to intense Ep-CAM staining of the biliary epithelium and focal co-staining with FP2 at the limiting plate of the portal tract (Fig. 5A). A liver sample with chronic rejection with paucity of the interlobular bile ducts, in turn, revealed CK-19 staining of the bile duct epithelium and co-staining with FP2 at the limiting plate and in some biliary structures (Fig. 5B). The post-transplantation liver sample showing features of acute rejection revealed co-staining of CK19 and FP2 at the limiting plate of the portal tracts (Fig. 5C). In the same liver specimen, we could also detect FP2-staining with co-staining of the biliary structures with MUC-1 (Fig. 5D).

Bottom Line: No specific staining was found at the stage of remodelled bile ducts.Polyductin was also co-localized in some DP cells together with oval stem cell markers.These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree, and support the following conclusions: (i) polyductin expression mirrors developmental properties of the primitive intrahepatic biliary system; (ii) polyductin is re-expressed in pathological conditions associated with DPM and (iii) polyductin might be a potential marker to distinguish CCC from HCC.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University of Innsbruck, Innsbruck, Austria.

ABSTRACT
The longest open reading frame of PKHD1 (polycystic kidney and hepatic disease 1), the autosomal recessive polycystic kidney disease (ARPKD) gene, encodes a single-pass, integral membrane protein named polyductin or fibrocystin. A fusion protein comprising its intracellular C-terminus, FP2, was previously used to raise a polyclonal antiserum shown to detect polyductin in several human tissues, including liver. In the current study, we aimed to investigate by immunohistochemistry the detailed polyductin localization pattern in normal (ductal plate [DP], remodelling ductal plate [RDP], remodelled bile ducts) and abnormal development of the primitive intrahepatic biliary system, known as ductal plate malformation (DPM). This work also included the characterization of polyductin expression profile in various histological forms of neonatal and infantile cholestasis, and in cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC). We detected polyductin expression in the intrahepatic biliary system during the DP and the RDP stages as well as in DPM. No specific staining was found at the stage of remodelled bile ducts. Polyductin was also detected in liver biopsies with neonatal cholestasis, including mainly biliary atresia and neonatal hepatitis with ductular reaction as well as congenital hepatic fibrosis. In addition, polyductin was present in CCC, whereas it was absent in HCC. Polyductin was also co-localized in some DP cells together with oval stem cell markers. These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree, and support the following conclusions: (i) polyductin expression mirrors developmental properties of the primitive intrahepatic biliary system; (ii) polyductin is re-expressed in pathological conditions associated with DPM and (iii) polyductin might be a potential marker to distinguish CCC from HCC.

Show MeSH
Related in: MedlinePlus