Genetic Analysis of Clinical Prostate Cancer

The general scope of this thesis is to assess molecular changes in prostate cancer cells. This is important because of two reasons: 1) knowledge of molecular changes may contribute to the understanding of prostate cancer development and lead to new therapies and 2) molecular changes may have prognostic value. Despite large changes in incidence and management of prostate cancer in the past decades, prostate cancer mortality has shown only minor changes. A modest drop in mortality is noted since 1992 in the USA [1]. For metastatic disease the corner stone of treatment remains hormonal therapy, originally described by Huggins and Hodges in 1941 [2]. This gives a response in most cases but after an average of 18 months hormone refractory disease develops. A better understanding of the molecular changes underlying prostate cancer is important to develop new, targeted therapies. The incidence of prostate cancer has markedly increased since the introduction of the PSA serum test in 1986. Many early cancers develop very slowly, and are clinically not relevant. To date, it is not possible to accurately indicate for which cancers immediate therapy is required. It is estimated that 17 patients have to undergo curative treatment in order to prevent 1 patient from dying of prostate cancer [3]. In a screening population this number is even higher. Accurate prognostic factors are urgently needed.