title: Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer.
abstract: BACKGROUND
  Special AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC) remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI) screening status, and SATB2 expression.
  
  
  METHODS
  Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmö Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearmans Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS) and overall survival (OS).
  
  
  RESULTS
  SATB1 was expressed in 222 (42%) CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16). SATB1 expression was significantly associated with microsatellite stable tumours (p < 0.001), beta-catenin overexpression (p < 0.001) and SATB2 expression (p < 0.001). While not prognostic in the full cohort, SATB1 expression was significantly associated with poor prognosis in SATB2 negative tumours (HR = 2.63; 95% CI 1.46-4.71; p(interaction) = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; p(interaction) = 0.015 for OS), remaining significant in multivariable analysis.
  
  
  CONCLUSIONS
  The results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta-catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and suggest prognostically antagonistic effects of SATB1 and SATB2. The mechanistic basis for these observations warrants further study.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1922643082772076.
authors.affiliation: Department of Clinical Sciences, Pathology, Lund University, Skåne University Hospital, Lund, SE, 221 85, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.forename: Henrik
authors.initials: H
authors.lastname: Johannesson
authors.forename: Sakarias
authors.initials: S
authors.lastname: Wangefjord
authors.forename: Darran P
authors.initials: DP
authors.lastname: O'Connor
authors.forename: Kajsa Ericson
authors.initials: KE
authors.lastname: Lindquist
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000032:analysis*; D053842:Microsatellite Instability; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis; D051176:beta Catenin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human; C521297:SATB2 protein, human; D014157:Transcription Factors; D051176:beta Catenin