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


Autoria(s): DORN, Livia; MENEZES, Luis F.; MIKUZ, Gregor; OTTO, Herwart F.; ONUCHIC, Luiz F.; SERGI, Consolato
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2009

Resumo

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.

Tyrolean Perinatal Program, Innsbruck, Austria

Osterreichische Krebshilfe Tirol (Austrian Cancer Research Tyrol)

Medical University of Innsbruck, Austria

Identificador

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v.13, n.7, p.1279-1290, 2009

1582-1838

http://producao.usp.br/handle/BDPI/21600

10.1111/j.1582-4934.2008.00519.x

http://dx.doi.org/10.1111/j.1582-4934.2008.00519.x

Idioma(s)

eng

Publicador

WILEY-BLACKWELL

Relação

Journal of Cellular and Molecular Medicine

Direitos

restrictedAccess

Copyright WILEY-BLACKWELL

Palavras-Chave #polyductin #fibrocystin #bile duct #ductal plate #hepatocellular carcinoma #cholangiocellular carcinoma #ARPKD #PKHD1 gene #POLYCYSTIC KIDNEY-DISEASE #MECKEL-SYNDROME #DUCTAL PLATE #BILE-DUCTS #ALAGILLE SYNDROME #EXPRESSION #ATRESIA #ARPKD #PROTEIN #PKHD1 #Cell Biology #Medicine, Research & Experimental
Tipo

article

original article

publishedVersion