The objective of this thesis was to explore the genetic changes and the genetic nature of prostate cancer progression using xenograft in vivo models and patient material and to seek out novel means to determine prognosis more accurately in prostate cancer patients after radical prostatectomy.

The xenografts studied resembled clinical prostate tumors in their chromosomal alterations. Chromosomal aberrations found in the xenografts and also in the metastases were generally similar compared to previously published chromosomal comparative genomic hybridization findings indicating the chromosomal regions harboring the most important oncogenes and tumor suppressor genes for prostate cancer. The strong clonal relationship between the metastases suggests that the selection of the lethal tumor clone already takes place at the time of cancer dissemination and the metastatic environment does not exert selection pressure on the metastatic clone. Androgen withdrawal seems to reduce the cell proliferation activity of prostate cancer cells for several months, but the majority of tumors emerging during the first withhold of castration are resistant to the subsequent rounds of castration in terms of cell proliferation activity. The biological aggressiveness of the tumor seems already to be defined at the time of diagnosis. Ki-67, EZH2 and MCM7 immunostainings and the combination of the latter two identified patients with a very high risk of recurrence after radical prostatectomy and could be useful in identifying patients for adjuvant therapy trials. Low Ki-67 immunostaining identified a subgroup of patients with a very low risk of disease progression, suggesting that such patients could be treated with active surveillance instead of immediate prostatectomy.

This thesis generated valuable information on the genetic changes and the genetic nature of prostate cancer progression and found novel approaches for more accurate determination of prostate cancer prognosis after radical prostatectomy.