Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma.

Background: While the Wnt pathway has been widely implicated in hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of beta-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 beta-catenin, the Ki67(+) proliferation fraction (PF), tumor size, grade, the Okuda stage and patient survival.