title: Prognostic Significance of Nuclear β-Catenin Expression in Patients with Colorectal Cancer from Iran.
abstract: BACKGROUND
  Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/β-catenin pathway. Accumulation of nuclear β-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear β-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC.
  
  
  OBJECTIVE
  In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated.
  
  
  METHODS
  In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear β-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant.
  
  
  RESULTS
  The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of β-catenin and 133 (80.6 %) were negative for β-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear β-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear β-catenin positive expression profile were found to be younger than patients with negative nuclear β-catenin expression (P = 0.010). Univariate and multivariate analysis showed that tumors with β-catenin expression had a poorer prognosis compared to tumors without β-catenin expression.
  
  
  CONCLUSIONS
  According to our findings, the distribution of nuclear b-catenin expression is a poor prognostic marker in patients with colon cancer.
authors.affiliation: Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nazemalhosseini Mojarad
authors.affiliation: Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Seyed Mohammad Hossein
authors.initials: SM
authors.lastname: Kashfi
authors.affiliation: Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Hanieh
authors.initials: H
authors.lastname: Mirtalebi
authors.affiliation: Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Shohre
authors.initials: S
authors.lastname: Almasi
authors.affiliation: Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Chaleshi
authors.affiliation: Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Roya
authors.initials: R
authors.lastname: Kishani Farahani
authors.affiliation: Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Peyman
authors.initials: P
authors.lastname: Tarban
authors.affiliation: Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Molaei
authors.affiliation: Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zali
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: J K Kuppen
keywords: Beta Catenin; Colorectal Cancer; Neoplasm Staging; Prognostic Biomarkers