title: Prognostic Significance of β-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series.
abstract: Robust biomarkers that can precisely stratify patients according to treatment needs are in great demand. The literature is inconclusive for most reported prognostic markers for colorectal cancer (CRC). Hence, adequately reported studies in large representative series are necessary to determine their clinical potential. We investigated the prognostic value of three Wnt signaling-associated proteins, β-catenin, E-cadherin, and SOX9, in a population-representative single-hospital series of 1290 Norwegian CRC patients by performing immunohistochemical analyses of each marker using the tissue microarray technology. Loss of membranous or cytosolic β-catenin and loss of cytosolic E-cadherin protein expression were significantly associated with reduced 5-year survival in 903 patients who underwent major resection (722 evaluable tissue cores) independently of standard clinicopathological high-risk parameters. Pre-specified subgroup analyses demonstrated particular effect for stage IV patients for β-catenin membrane staining (P = 0.018; formal interaction test P = 0.025). Among those who underwent complete resection (714 patients, 568 evaluable), 5-year time-to-recurrence analyses were performed, and stage II patients with loss of cytosolic E-cadherin were identified as an independent high-risk subgroup (P = 0.020, formal interaction test was not significant). Nuclear β-catenin and SOX9 protein, regardless of intracellular location, were not associated with prognosis. In conclusion, the protein expression level of membranous or cytosolic β-catenin and E-cadherin predicts CRC patient subgroups with inferior prognosis.
authors.affiliation: Department for Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway ; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo , Oslo , Norway.
authors.forename: Jarle
authors.initials: J
authors.lastname: Bruun
authors.affiliation: Department for Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway ; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo , Oslo , Norway.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kolberg
authors.affiliation: Department of Pathology, Oslo University Hospital , Oslo , Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Pathology, Oslo University Hospital , Oslo , Norway ; Faculty of Medicine, University of Oslo , Oslo , Norway.
authors.forename: Aud
authors.initials: A
authors.lastname: Svindland
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo , Oslo , Norway ; Faculty of Medicine, University of Oslo , Oslo , Norway ; Department of Gastrointestinal Surgery, Aker Hospital, Oslo University Hospital , Oslo , Norway.
authors.forename: Arild
authors.initials: A
authors.lastname: Nesbakken
authors.affiliation: Department for Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway ; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo , Oslo , Norway ; Department of Molecular Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo , Oslo , Norway.
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
keywords: E-cadherin; SOX9 transcription factor; beta-catenin; biomarker discovery; colorectal cancer; guideline adherence; prognostic biomarkers