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Coordinated expression of cyclin D1 and LEF‐1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma
Author(s) -
SchmittGraeff Annette,
ErteltHeitzmann Viktoria,
Allgaier HansPeter,
Olschewski Manfred,
Nitschke Roland,
Haxelmans Sabine,
Koelble Konrad,
Behrens Jürgen,
Blum Hubert Erich
Publication year - 2005
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2005.01069.x
Subject(s) - cyclin d1 , hccs , cancer research , wnt signaling pathway , biology , cyclin d , hepatocellular carcinoma , cyclin , cyclin b , transcription factor , cyclin a2 , immunohistochemistry , cell cycle , microbiology and biotechnology , cell , signal transduction , gene , immunology , genetics
Background: While the Wnt pathway has been widely implicated in hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of β‐catenin‐lymphoid enhancer factor‐1 (LEF‐1)/T‐cell factor (TCF) signaling is controversely discussed. Methods: By immunohistochemical analyses we studied the subcellular localization of LEF‐1/TCF and cyclin D1 in 162 hepatocellular carcinoma (HCC). Single‐ and double‐label imaging by brightfield and confocal laser scanning microscopy was quantitated and correlated with β‐catenin, the Ki67 + proliferation fraction (PF), tumor size, grade, the Okuda stage and patient survival. Results: The frequency of nuclear cyclin D1 expression was 28% and closely correlated with LEF‐1/TCF ( P <0.0001) and the Ki67 + PF ( P =0.03). Nuclear LEF‐1/TCF expression was observed in 52% of all cases, but was also present in 42% of cyclin D1 − cases. Nuclear β‐catenin was identified in 37% of all HCCs and correlated with LEF‐1/TCF ( P =0.04). The expression of cyclin D1, LEF‐1/TCF or β‐catenin did not correlate with other clinico‐pathological data. Conclusions: A large proportion of HCCs does not appear to be linked to a deregulation of cyclin D1. However, the coordinated expression of cyclin D1 and LEF‐1/TCF in some cases suggests the role of cyclin D1 as a Wnt target gene in a subset of HCCs.