caa a22 4500 445331348 CHVBK 20180317142738.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10689-010-9406-x doi (NATIONALLICENCE)springer-10.1007/s10689-010-9406-x Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer [Elektronische Daten] [Anna Isinger-Ekstrand, Christina Therkildsen, Inge Bernstein, Mef Nilbert] The Wnt signaling pathway is frequently deranged in colorectal cancer and is a key target for future preventive and therapeutic approaches. Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are characterized by wide-spread microsatellite instability, but show few gross genomic alterations. We characterized expression of the Wnt signaling pathway markers β-catenin, E-cadherin, TCF-4, and PTEN using immunohistochemical staining in colorectal cancers from individuals with HNPCC. Reduced membranous staining for β-catenin was found in 64% and for E-cadherin in 80% with strong correlation between these markers (P=0.001). Nuclear β-catenin staining was detected in 19% of the tumors. Overexpression of TCF-4, which is activated by β-catenin, was found in 89% and downregulation of PTEN, which suppresses nuclear accumulation of β-catenin, was present in 54% of the tumors. In summary, altered expression of target molecules in the Wnt signaling pathway was demonstrated in the vast majority of the HNPCC-associated tumors, which support deranged Wnt-signaling as a central tumorigenic mechanism also in MMR defective colorectal cancer. Springer Science+Business Media B.V., 2010 β-catenin nationallicence E-cadherin nationallicence HNPCC nationallicence Lynch syndrome nationallicence PTEN nationallicence TCF-4 nationallicence Wnt signaling nationallicence HNPCC : Hereditary nonpolyposis colorectal cancer nationallicence IHC : Immunohistochemistry nationallicence MMR : Mismatch repair nationallicence Isinger-Ekstrand Anna Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden aut Therkildsen Christina Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark aut Bernstein Inge HNPCC-Register, Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark aut Nilbert Mef Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden aut Familial Cancer Springer Netherlands 10/2(2011-06-01), 239-243 1389-9600 10:2<239 2011 10 10689 https://doi.org/10.1007/s10689-010-9406-x text/html Onlinezugriff via DOI 1 brief-communication jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-010-9406-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Isinger-Ekstrand Anna Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden aut NATIONALLICENCE 700 1- Therkildsen Christina Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Bernstein Inge HNPCC-Register, Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark aut NATIONALLICENCE 700 1- Nilbert Mef Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/2(2011-06-01), 239-243 1389-9600 10:2<239 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer