title: Expression and localization of axin 2 in colorectal carcinoma and its clinical implication.
abstract: OBJECTIVE
  Aberrant activation of the Wnt/β-catenin pathway plays a major role in the development of colorectal carcinoma (CRC). Axin 2 is a key protein of this pathway and is upregulated in CRC. Here, we investigated RNA- and protein expression of axin 2 in CRC tissues at the single cell level. Moreover, the association of axin 2 with prognosis and survival was investigated in a large cohort of CRC patients (n = 280).
  
  
  METHODS
  Localization and expression of axin 2 and β-catenin was investigated using in situ hybridization and immunohistochemical staining. The quantitative expression levels of axin 2 were determined using RT-qPCR. The association of axin 2 expression with prognosis and survival of the patients was determined by statistical analysis (logrank test, Kaplan-Meier).
  
  
  RESULTS
  Our results confirmed the upregulation of axin 2 in CRC and showed that it is broadly expressed in the cytoplasm of the tumor epithelial cells both, in the tumor center and at the invasion front. Axin 2 was rarely expressed by tumor stromal cells and only weakly by normal colonic epithelial cells. Staining of β-catenin and axin 2 in consecutive CRC tissue sections revealed that nuclear translocation of β-catenin in the tumor front was not associated with changes in the cytoplasmic localization of axin 2. Axin 2 did not show any association with proven prognostic factors or survival of the CRC patients.
  
  
  CONCLUSIONS
  The generally increased expression of axin 2 in all tumor stages as compared to normal tissue suggests an initiating pathogenic function in the development of CRC.
authors.affiliation: Division of Molecular and Experimental Surgery, University Medical Center Erlangen, Erlangen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Schaal
authors.forename: Sandra
authors.initials: S
authors.lastname: Grenz
authors.forename: Susanne
authors.initials: S
authors.lastname: Merkel
authors.forename: Tilman T
authors.initials: TT
authors.lastname: Rau
authors.forename: Michel V
authors.initials: MV
authors.lastname: Hadjihannas
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Priya
authors.initials: P
authors.lastname: Chudasama
authors.forename: Roland S
authors.initials: RS
authors.lastname: Croner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Behrens
authors.forename: Michael
authors.initials: M
authors.lastname: Stürzl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Naschberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060466:Axin Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000378:metabolism
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D051176:beta Catenin