TCF-3, 4 protein expression correlates with β-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers

• Published in: International journal of colorectal disease Vol. 25; no. 8; pp. 931 - 939
• Main Authors: Balaz, Peter, Plaschke, Jens, Krüger, Stefan, Görgens, Heike, Schackert, Hans K.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2010; Springer
• Subjects: Adenomatous Polyposis Coli Protein - metabolism; Antibodies, Monoclonal - immunology; beta Catenin - metabolism; Biological and medical sciences; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Hepatology; Humans; Immunohistochemistry; Internal Medicine; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Medical sciences; Medicine; Medicine & Public Health; Microsatellite Instability; Original Article; Proctology; Staining and Labeling; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; TCF Transcription Factors - metabolism; Transcription Factor 7-Like 1 Protein; Transcription Factor 7-Like 2 Protein; Tumors; β-catenin; Microsatellite stable and unstable cancers; TCF-3; Sporadic; 4; HNPCC colorectal cancers; Human; TCF-3 - 4; Hereditary nonpolyposis colorectal cancer; Rectal disease; Colorectal cancer; Malignant tumor; Protein; Genetic disease; Colonic disease; Microsatellite DNA; β Catenin; Gastroenterology; Digestive diseases; Intestinal disease; Cancer
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-010-0959-9

Purpose The β-catenin–T-cell factor-4 (TCF-4) complex is the main control switch of cell proliferation and differentiation of normal and malignant intestinal cells. The aim of our study was to analyze the protein expression of components of the Wnt pathway in microsatellite stable (MSS) and highly unstable (MSI-H) sporadic and hereditary nonpolyposis colorectal cancer (HNPCC) in human colorectal cancers. Methods Sixty seven colorectal tumors comprising of 15 sporadic MSS, 12 sporadic microsatellite instability colorectal tumors and 40 tumors from HNPCC patients, of which 20 were MSS and 20 MSI-H, were analyzed for the expression of APC, β-catenin, and TCF-3, 4 proteins by immunohistochemistry. Results We found a significant difference in cytoplasmic APC expression frequency between sporadic MSS (52%) and HNPCC tumors (78%), whereas no difference was detected between MSI-H and MSS or HNPCC tumors. All tumor groups showed a similar pattern of decreased membranous staining and increased cytoplasmic and nuclear staining for β-catenin compared to normal cells. Moreover, the TCF-3, 4 protein expression was higher (43%) in HNPCC-associated MSS tumors compared to sporadic tumors (14%; analysis of variance (ANOVA) p  < 0.05). For HNPCC tumors, the subcellular β-catenin expression (membranous, cytoplasmic, and nuclear) correlated with the nuclear TCF-3, 4 signal in MSS tumors (Spearman correlation p  < 0.0007) and MSI-H tumors (Spearman correlation p  < 0.0001). Conclusion We have shown a previously unknown difference in TCF-3, 4 protein expression between sporadic and HNPCC MSS tumors. In addition, we found no difference in nuclear β-catenin signal intensity, which may be caused by an alteration in Wnt pathway in MSS sporadic tumors by unknown mechanisms leading to lower TCF-3, 4 protein expression. This hypothesis has to be tested in future investigations.