PMID- 15998435 OWN - NLM STAT- MEDLINE DCOM- 20051101 LR - 20151119 IS - 1478-3223 (Print) IS - 1478-3223 (Linking) VI - 25 IP - 4 DP - 2005 Aug TI - Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma. PG - 839-47 AB - 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. 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 beta-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 beta-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. FAU - Schmitt-Graeff, Annette AU - Schmitt-Graeff A AD - Institute of Pathology, University of Freiburg, Freiburg, Germany. ahsg@ukl.uni-freiburg.de FAU - Ertelt-Heitzmann, Viktoria AU - Ertelt-Heitzmann V FAU - Allgaier, Hans-Peter AU - Allgaier HP FAU - Olschewski, Manfred AU - Olschewski M FAU - Nitschke, Roland AU - Nitschke R FAU - Haxelmans, Sabine AU - Haxelmans S FAU - Koelble, Konrad AU - Koelble K FAU - Behrens, Jurgen AU - Behrens J FAU - Blum, Hubert Erich AU - Blum HE LA - eng PT - Journal Article PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (Biomarkers, Tumor) RN - 0 (CTNNB1 protein, human) RN - 0 (Cytoskeletal Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Ki-67 Antigen) RN - 0 (LEF1 protein, human) RN - 0 (Lymphoid Enhancer-Binding Factor 1) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (beta Catenin) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/metabolism MH - Carcinoma, Hepatocellular/*metabolism/mortality/pathology MH - Cell Nucleus/metabolism/pathology MH - Child MH - Cyclin D1/*metabolism MH - Cytoskeletal Proteins/metabolism MH - DNA-Binding Proteins/*metabolism MH - Female MH - Fluorescent Antibody Technique MH - Humans MH - Image Processing, Computer-Assisted MH - Immunohistochemistry MH - Ki-67 Antigen/metabolism MH - Liver Neoplasms/*metabolism/mortality/pathology MH - Lymphoid Enhancer-Binding Factor 1 MH - Male MH - Microscopy, Confocal MH - Middle Aged MH - Survival Rate MH - Trans-Activators/metabolism MH - Transcription Factors/*metabolism MH - beta Catenin EDAT- 2005/07/07 09:00 MHDA- 2005/11/03 09:00 CRDT- 2005/07/07 09:00 PHST- 2005/07/07 09:00 [pubmed] PHST- 2005/11/03 09:00 [medline] PHST- 2005/07/07 09:00 [entrez] AID - LIV1069 [pii] AID - 10.1111/j.1478-3231.2005.01069.x [doi] PST - ppublish SO - Liver Int. 2005 Aug;25(4):839-47. doi: 10.1111/j.1478-3231.2005.01069.x.