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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 adult hepatobiliary carcinomas. (A) is the microphotograph of a cholangiocellular carcinoma (CCC) showing a moderate to intense FP2 staining of the neoplastic epithelium (arrowheads) embedded in a dense stroma (anti-FP2, ×200); in (B) there is a moderate FP2 staining in another CCC (arrowheads) (anti-FP2, ×400); in (C) no FP2 staining is demonstrated in a hepatocellular carcinoma (HCC) with trabecular growth pattern (anti-FP2, ×100), (D) no FP2 staining is also observed in another HCC with pseudoglandular growth pattern (anti-FP2, ×200), and (E and F) show tumour tissue metastasis to the lung from the liver combining cholangiocarcinomatous and hepatocellular features and showing FP2 staining mostly in cholangiocarcinomatous cells (E) (arrowheads) (anti-FP2, ×400).
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fig04: Polyductin expression in adult hepatobiliary carcinomas. (A) is the microphotograph of a cholangiocellular carcinoma (CCC) showing a moderate to intense FP2 staining of the neoplastic epithelium (arrowheads) embedded in a dense stroma (anti-FP2, ×200); in (B) there is a moderate FP2 staining in another CCC (arrowheads) (anti-FP2, ×400); in (C) no FP2 staining is demonstrated in a hepatocellular carcinoma (HCC) with trabecular growth pattern (anti-FP2, ×100), (D) no FP2 staining is also observed in another HCC with pseudoglandular growth pattern (anti-FP2, ×200), and (E and F) show tumour tissue metastasis to the lung from the liver combining cholangiocarcinomatous and hepatocellular features and showing FP2 staining mostly in cholangiocarcinomatous cells (E) (arrowheads) (anti-FP2, ×400).

Mentions: Finally, we analysed two types of liver carcinomas: 16 cases of HCC and 23 cases of CCC. Hep Par 1 was negative in all CCC cases. Hep Par 1 was positive in 12 of 16 HCC. In addition, an extensive clinical radiological workup also helped to exclude metastatic adenocarcinoma. Twenty-two CCC cases showed positive staining for polyductin in malignant ductular proliferations (Fig. 4A and B), whereas the surrounding normal hepatocytes were negative or showed slight baseline staining only. FP2 staining was weak in nine cases (poorly differentiated CCC), moderate in seven (moderately differentiated CCC) and intense in six well-differentiated CCC. One CCC case did not show any staining, although different unmasking procedures were performed. This FP2 negative case showed very poor differentiation.


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 adult hepatobiliary carcinomas. (A) is the microphotograph of a cholangiocellular carcinoma (CCC) showing a moderate to intense FP2 staining of the neoplastic epithelium (arrowheads) embedded in a dense stroma (anti-FP2, ×200); in (B) there is a moderate FP2 staining in another CCC (arrowheads) (anti-FP2, ×400); in (C) no FP2 staining is demonstrated in a hepatocellular carcinoma (HCC) with trabecular growth pattern (anti-FP2, ×100), (D) no FP2 staining is also observed in another HCC with pseudoglandular growth pattern (anti-FP2, ×200), and (E and F) show tumour tissue metastasis to the lung from the liver combining cholangiocarcinomatous and hepatocellular features and showing FP2 staining mostly in cholangiocarcinomatous cells (E) (arrowheads) (anti-FP2, ×400).
© Copyright Policy
Related In: Results  -  Collection

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

fig04: Polyductin expression in adult hepatobiliary carcinomas. (A) is the microphotograph of a cholangiocellular carcinoma (CCC) showing a moderate to intense FP2 staining of the neoplastic epithelium (arrowheads) embedded in a dense stroma (anti-FP2, ×200); in (B) there is a moderate FP2 staining in another CCC (arrowheads) (anti-FP2, ×400); in (C) no FP2 staining is demonstrated in a hepatocellular carcinoma (HCC) with trabecular growth pattern (anti-FP2, ×100), (D) no FP2 staining is also observed in another HCC with pseudoglandular growth pattern (anti-FP2, ×200), and (E and F) show tumour tissue metastasis to the lung from the liver combining cholangiocarcinomatous and hepatocellular features and showing FP2 staining mostly in cholangiocarcinomatous cells (E) (arrowheads) (anti-FP2, ×400).
Mentions: Finally, we analysed two types of liver carcinomas: 16 cases of HCC and 23 cases of CCC. Hep Par 1 was negative in all CCC cases. Hep Par 1 was positive in 12 of 16 HCC. In addition, an extensive clinical radiological workup also helped to exclude metastatic adenocarcinoma. Twenty-two CCC cases showed positive staining for polyductin in malignant ductular proliferations (Fig. 4A and B), whereas the surrounding normal hepatocytes were negative or showed slight baseline staining only. FP2 staining was weak in nine cases (poorly differentiated CCC), moderate in seven (moderately differentiated CCC) and intense in six well-differentiated CCC. One CCC case did not show any staining, although different unmasking procedures were performed. This FP2 negative case showed very poor differentiation.

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