AIMS: 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). CONCLUSION: 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.
AIMS: 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). CONCLUSION: 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: B M Ghadimi; D L Sackett; M J Difilippantonio; E Schröck; T Neumann; A Jauho; G Auer; T Ried Journal: Genes Chromosomes Cancer Date: 2000-02 Impact factor: 5.006
Authors: N Sato; K Mizumoto; M Nakamura; K Nakamura; M Kusumoto; H Niiyama; T Ogawa; M Tanaka Journal: Clin Cancer Res Date: 1999-05 Impact factor: 12.531
Authors: Kai Neben; Björn Tews; Gunnar Wrobel; Meinhard Hahn; Felix Kokocinski; Christian Giesecke; Ulf Krause; Anthony D Ho; Alwin Krämer; Peter Lichter Journal: Oncogene Date: 2004-03-25 Impact factor: 9.867
Authors: Michelle S Levine; Bjorn Bakker; Bram Boeckx; Julia Moyett; James Lu; Benjamin Vitre; Diana C Spierings; Peter M Lansdorp; Don W Cleveland; Diether Lambrechts; Floris Foijer; Andrew J Holland Journal: Dev Cell Date: 2017-01-26 Impact factor: 12.270