Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Centrosome abnormalities in prostate carcinoma are more extensive in high Gleason grade tumors and correlate with chromosome instability

G Pihan MD 1, J Wallace 1, A Purohit PhD 2, SJ Doxsey PhD 2, R Malhotra MD 1

Departments of Pathology, a and Molecular Medicine, b University of Massachusetts Medical School, Worcester, MA,

AIMS: Because centrosomes control the fidelity of mitotic chromosome segregation cell shape and form and because both aneuploidy and cytologic anaplasia have been previously shown to be an adverse prognostic factor in prostate cancer we have studied centrosome characteristics in invasive prostate carcinoma. METHODS: Using immunocytochemistry, the distribution of pericentrin was studied on paraffin sections from 121 radical prostatectomies containing invasive cancer. Quantitative digital imaging was used to determine the number, size, and content of pericentrin of centrosomes as well as non-centrosomal pericentrin in paired normal and tumor glands. The copy number of chromosomes 1 and 8 was determined by bright-field in-situ hybridization with centromere-specific probes. RESULTS: We observed that most prostate carcinomas had at least two, and often more, abnormal centrosome features. The number as well as the amount of pericentrin at the centrosome and elsewhere increased with increasing Gleason grade. There was a good correlation between the extent of centrosome abnormalities and the degree of CIN. Artificial elevation of pericentrin in prostate epithelial cells lines increased cytologic anaplasia and exacerbated CIN. CONCLUSIONS: Centrosomes are abnormal in the majority of invasive prostate carcinomas and the extent of such abnormalities correlates directly with the cytologic grade of the cancer and with the extent of CIN. Specific induction of centrosome abnormalities in prostate epithelial cells can induce many of the cytologic and karyologic features of high grade prostate carcinoma. Centrosome dysfunction may play a critical role in the progression of prostate cancer from an indolent to and aggressive, often lethal, disease.

KEY WORDS: ploidy genetic instability genomic instability.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.