Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma

J. Halász, Ágnes Holczbauer, C. Páska, M. Kovács, Gábor Benyó, Tibor Verebély, Z. Schaff, András Kiss

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Claudins (CLDNs), a family of transmembrane proteins, are major constituents of tight junctions (TJs). They have been shown to be differentially regulated in malignant tumors and play a role in carcinogenesis and progression. We aimed to explain the molecular mechanism underlying the main epithelial components of hepatoblastomas (HBs) based on the composition of TJs. Fourteen formalin-fixed, paraffin-embedded surgical resection specimens were analyzed by immunohistochemistry for CLDN-1, -2, -3, -4, -7; proliferating cell nuclear antigen (PCNA); Ki-67; β-catenin; cytokeratin-7 (CK-7); and hepatocyte-specific antigen; messenger RNA was isolated for real-time reverse transcriptase polymerase chain reaction analysis of the CLDNs from dissected fetal and embryonal cell types. Significantly increased protein and messenger RNA expression of CLDN-1 and -2 was detected in the fetal compared with the embryonal component. Both cell types displayed negative or weak immunostainings for CLDN-3, -4, and -7. Hepatocyte-specific antigen was dominantly expressed in the fetal component. PCNA and Ki-67 labeling indices were significantly higher in embryonal compared with fetal cells. β-catenin cytoplasmic/nuclear immunoreaction was frequent, although not showing significant differences between fetal and embryonal cells. Mutational analysis of β-catenin detected mutation in two cases. Our results suggest that increased expression of CLDN-1 and -2 characterizes the more differentiated fetal component in HBs and is a reliable marker for differentiating fetal and embryonal cell types in HBs. The results proved that the embryonal and fetal components of HBs differ in such important feature as the protein composition of TJs. The expression of CLDN-1 and -2 is inversely correlated with cell proliferation. The more aggressive, rapidly proliferating embryonal phenotype is associated with the decrease/loss of CLDN-1 and -2. However, there are no data indicating association with the nuclear translocation of β-catenin.

Original languageEnglish
Pages (from-to)555-561
Number of pages7
JournalHuman Pathology
Volume37
Issue number5
DOIs
Publication statusPublished - May 2006

Fingerprint

Claudin-2
Claudins
Claudin-1
Hepatoblastoma
Catenins
Tight Junctions
Proliferating Cell Nuclear Antigen
Hepatocytes
Keratin-7
Tight Junction Proteins
Antigens
Messenger RNA
Reverse Transcriptase Polymerase Chain Reaction
Paraffin
Formaldehyde
Real-Time Polymerase Chain Reaction
Carcinogenesis
Proteins
Immunohistochemistry
Cell Proliferation

Keywords

  • Claudins
  • Differentiation
  • Hepatoblastoma
  • Liver
  • Tight junction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma. / Halász, J.; Holczbauer, Ágnes; Páska, C.; Kovács, M.; Benyó, Gábor; Verebély, Tibor; Schaff, Z.; Kiss, András.

In: Human Pathology, Vol. 37, No. 5, 05.2006, p. 555-561.

Research output: Contribution to journalArticle

Halász, J. ; Holczbauer, Ágnes ; Páska, C. ; Kovács, M. ; Benyó, Gábor ; Verebély, Tibor ; Schaff, Z. ; Kiss, András. / Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma. In: Human Pathology. 2006 ; Vol. 37, No. 5. pp. 555-561.
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