Correlation of centrosomal aberrations with cell differentiation and DNA ploidy in prostate cancer

摘要

OBJECTIVE: To analyze the centrosomal abnormalities in correlation with DNA ploidy and clinicopathologic data in prostate cancer. STUDY DESIGN: Formalin-fixed, paraffin-embedded material from 63 prostate cancers (PCa) and 10 normal control cases were studied. Centrosomal features (number, area and shape) were assessed by immunohistochemistry with a gamma-tubulin monoclonal antibody. For each case centrosomal features were assessed in 100 cells, and the mean and median value was calculated. Statistical analysis was done by Student's t test, Mann-Whitney U test and multivariate analysis. The colocalization of gamma-tubulin and pericentrin at the centrosome was proven by double immunofluorescence staining. The DNA ploidy status was analyzed on Feulgen-stained, disintegrated paraffin sections using the OPTIMAS-based work station (Media Cybernetics, Silver Spring, Maryland, U.S.A.). RESULTS: PCa cells showed centrosomal aberrations when compared to normal tissue. Poorly differentiated PCa showed more centrosomal abnormalities than well differentiated PCa (p<0.05). Twenty-seven percent PCa were DNA nondiploid and 73% PCa were DNA diploid, respectively, just as all control specimens. DNA nondiploid status correlates with centrosomal abnormalities (p<0.05). pT4 tumors showed significantly more centrosomes than pT2 and pT3 tumors (p<0.05). CONCLUSION: Changes in centrosome features indicate disturbed centrosome function and are significantly correlated with loss of differentiation in PCa. This is the first image analysis study of centrosome features in PCa, confirming that centrosome defects are involved in the acquisition of chromosomal aberrations in PCa.