title: Numerical and structural centrosome aberrations are an early and stable event in the adenoma-carcinoma sequence of colorectal carcinomas.
abstract: OBJECTIVE
  Numerical and structural centrosome changes have been described for and linked with genetic instability in solid tumors. Here, we specifically address centrosome aberrations in the adenoma-carcinoma sequence of colorectal cancer by detailed evaluation of gamma-tubulin staining patterns.
  
  
  METHODS
  Formalin-fixed and paraffin-embedded specimens (normal colonic epithelium n=21; low-grade intraepithelial neoplasia n=27, high-grade intraepithelial neoplasia n=16 and invasive adenocarcinomas n=33) were stained by an anti-gamma-tubulin antibody using standard immunofluorescence. Three-dimensional image stacks of the stainings were recorded (Zeiss LSM510 confocal microscope), followed by numerical and structural data analysis (DIAS software package) and statistical evaluation (NCSS-software).
  
  
  RESULTS
  The mean centrosome signal per cell differed significantly (P<0.0001) between normal colonic epithelium (0.8775) and each low-grade intraepithelial neoplasia (1.787), high-grade intraepithelial neoplasia (2.259) and invasive carcinomas (2.267). Similarly, both the centrosomes' structural entropy (SE) and minimal spanning tree (MST) differed significantly (P<0.001) between normal (SE=3.956, MST=38.78) and each low- (SE=6.39, MST=26) and high-grade intraepithelial neoplasia (SE=5.75, MST=26.97) and invasive carcinoma (SE=6.86, MST=28.08).
  
  
  CONCLUSIONS
  Numerical and structural centrosome dysregulation is seen as early as in low-grade dysplastic lesions of the adenoma-carcinoma sequence of colorectal carcinomas and may, as such, play an initial role in the carcinogenic process.
authors.affiliation: Institute of Pathology, University Hospital Freiburg, Germany.
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gerlach
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.forename: Roland
authors.initials: R
authors.lastname: Nitschke
authors.forename: Sabine
authors.initials: S
authors.lastname: Haxelmans
authors.forename: Klaus
authors.initials: K
authors.lastname: Kayser
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopt
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018385:Centrosome; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018613:Microscopy, Confocal; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D014404:Tubulin