Analysis of genetic changes underlying local recurrence of prostate carcinoma during androgen deprivation therapy

Pasi Koivisto, Eija Hyytinen, Christian Palmberg, Teuvo Tammela, Tapio Visakorpi, Jorma Isola, Olli P. Kallioniemi

    Research output: Contribution to journalArticleScientificpeer-review

    47 Citations (Scopus)

    Abstract

    The molecular mechanisms and genetic changes that lead to the progression of prostate cancer during endocrine therapy are poorly characterized. Here, paired specimens from both untreated primary tumors and from local recurrences were collected from 10 prostate cancer patients treated by conventional androgen deprivation therapy. The genetic progression of the tumors was studied by using interphase fluorescence in situ 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 chromosome copy number variability from one cell to another. Increased copy number of chromosome X was particularly common in the recurrent tumors. In addition, specific high level amplification of the androgen receptor (AR) gene (Xq12) was detected in three highly aneuploid recurrent tumors. Our findings suggest that hormone- refractory prostate cancers are genetically very complex and show intratumor genetic heterogeneity. 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 recurrence.

    Original languageEnglish
    Pages (from-to)1608-1614
    Number of pages7
    JournalAmerican journal of pathology
    Volume147
    Issue number6
    Publication statusPublished - Dec 1995
    Publication typeA1 Journal article-refereed

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine

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