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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 in foetal liver without and with ductal plate malformation. In (A), there is a portal tract at the stage of ductal plate with intense staining (arrows) of the hepatocytes at the limiting plate (anti-FP2, ×400); (B) shows a remodelling ductal plate structure with a gradient of staining intensity: the intensity is greater close to the periportal hepatocytes (long arrow) than close to the duct or in the remodelling bile duct (short arrow) (anti-FP2, ×400); (C) shows no staining of the remodelled bile duct (arrow) (anti-FP2, ×200). A baseline staining is present in the hepatocytes; (D) shows a liver of foetus with Meckel syndrome and ductal plate malformation with intense staining of the abnormal biliary structures (arrowheads) close to the periportal hepatocytes (anti-FP2, ×200).
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fig01: Polyductin expression in foetal liver without and with ductal plate malformation. In (A), there is a portal tract at the stage of ductal plate with intense staining (arrows) of the hepatocytes at the limiting plate (anti-FP2, ×400); (B) shows a remodelling ductal plate structure with a gradient of staining intensity: the intensity is greater close to the periportal hepatocytes (long arrow) than close to the duct or in the remodelling bile duct (short arrow) (anti-FP2, ×400); (C) shows no staining of the remodelled bile duct (arrow) (anti-FP2, ×200). A baseline staining is present in the hepatocytes; (D) shows a liver of foetus with Meckel syndrome and ductal plate malformation with intense staining of the abnormal biliary structures (arrowheads) close to the periportal hepatocytes (anti-FP2, ×200).

Mentions: Liver tissue from seven foetuses without intra- and extrahepatic biliary system abnormalities was initially examined. In the DP stage (Fig. 1A), FP2 staining was diffusely more intense in the hepatocytes close to the portal vein in most cases (six out of seven), whereas a faint staining was detected in one case. A faint staining was present in almost all hepatocytes at this stage. In RDP stage, FP2 staining was slightly more variable. The remodelling biliary structures (Fig. 1B) showed an intense staining in one liver sample, a weak labelling signal in four liver samples, and no staining in two liver samples. A faint staining was also present in almost all hepatocytes at this stage. Remodelled biliary structures of the portal tracts at RBD stage (Fig. 1C) remained unstained in all cases and a very faint staining was detected in the hepatocytes of these liver samples. Liver tissue from four foetuses affected with Meckel syndrome (Fig. 1D) was then investigated and showed intense labelling of the abnormally remodelling biliary structures as seen in DP stage during the normal development of the intrahepatic biliary system. A faint staining was also present in almost all hepatocytes of these liver samples.


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 in foetal liver without and with ductal plate malformation. In (A), there is a portal tract at the stage of ductal plate with intense staining (arrows) of the hepatocytes at the limiting plate (anti-FP2, ×400); (B) shows a remodelling ductal plate structure with a gradient of staining intensity: the intensity is greater close to the periportal hepatocytes (long arrow) than close to the duct or in the remodelling bile duct (short arrow) (anti-FP2, ×400); (C) shows no staining of the remodelled bile duct (arrow) (anti-FP2, ×200). A baseline staining is present in the hepatocytes; (D) shows a liver of foetus with Meckel syndrome and ductal plate malformation with intense staining of the abnormal biliary structures (arrowheads) close to the periportal hepatocytes (anti-FP2, ×200).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496142&req=5

fig01: Polyductin expression in foetal liver without and with ductal plate malformation. In (A), there is a portal tract at the stage of ductal plate with intense staining (arrows) of the hepatocytes at the limiting plate (anti-FP2, ×400); (B) shows a remodelling ductal plate structure with a gradient of staining intensity: the intensity is greater close to the periportal hepatocytes (long arrow) than close to the duct or in the remodelling bile duct (short arrow) (anti-FP2, ×400); (C) shows no staining of the remodelled bile duct (arrow) (anti-FP2, ×200). A baseline staining is present in the hepatocytes; (D) shows a liver of foetus with Meckel syndrome and ductal plate malformation with intense staining of the abnormal biliary structures (arrowheads) close to the periportal hepatocytes (anti-FP2, ×200).
Mentions: Liver tissue from seven foetuses without intra- and extrahepatic biliary system abnormalities was initially examined. In the DP stage (Fig. 1A), FP2 staining was diffusely more intense in the hepatocytes close to the portal vein in most cases (six out of seven), whereas a faint staining was detected in one case. A faint staining was present in almost all hepatocytes at this stage. In RDP stage, FP2 staining was slightly more variable. The remodelling biliary structures (Fig. 1B) showed an intense staining in one liver sample, a weak labelling signal in four liver samples, and no staining in two liver samples. A faint staining was also present in almost all hepatocytes at this stage. Remodelled biliary structures of the portal tracts at RBD stage (Fig. 1C) remained unstained in all cases and a very faint staining was detected in the hepatocytes of these liver samples. Liver tissue from four foetuses affected with Meckel syndrome (Fig. 1D) was then investigated and showed intense labelling of the abnormally remodelling biliary structures as seen in DP stage during the normal development of the intrahepatic biliary system. A faint staining was also present in almost all hepatocytes of these liver samples.

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