ANALYSIS OF GENETIC CHANGES UNDERLYING LOCAL RECURRENCE OF PROSTATE CARCINOMA DURING ANDROGEN DEPRIVATION THERAPY

The molecular mechanisms and genetic changes that lead to the progress ion of prostate cancer during endocrine therapy are poorly characteriz ed. Here, paired specimens from both untreated primary tumors and from local recurrences were collected from 10 prostate cancer patients tre ated by conventional androgen deprivation therapy. The genetic progres sion of the tumors was studied by using interphase fluorescence in sit u hybridization and chromosome-specific probes. Six primary tumors (60 %) and all ten recurrent tumors were aneuploid by fluorescence in situ hybridization. The recurrent tumors also showed a high degree of chro mosome copy number variability from one cell to another. Increased cop y number of chromosome X was particularly common in the recurrent tumo rs. In addition, specific high level amplification of the androgen rec eptor (AR) gene (Xq12) was detected in three highly aneuploid recurren t tumors. Our findings suggest that hormone-refractory prostate cancer s are genetically very complex and show intratumor genetic heterogenei ty. Increased copy number of chromosome X and the amplification of the androgen receptor (AR) gene may confer proliferative advantage during androgen deprivation and thus contribute to the development of recurr ence.