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Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma

Oncogene volume 22, pages 1978–1987 (2003)Cite this article

Abstract

Mechanisms underlying prostate cancer (CaP) initiation and progression are poorly understood. A chromosomal instability mechanism leading to the generation of numerical and structural chromosomal changes has been implicated in the preneoplastic and neoplastic stages of CaP. Telomere dysfunction is one potential mechanism associated with the onset of such instability. To determine whether there was alteration in telomere length and chromosome number, 15 paraffin-embedded prostatectomy specimens were investigated using quantitative peptide nucleic acid (PNA) FISH analysis of representative foci of carcinoma, putative precancerous lesions (high-grade prostatic intraepithelial neoplasia, HPIN) and nondysplastic prostate epithelium. A significant decrease in telomere length was shown in both HPIN and CaP in comparison with normal epithelium. In addition, elevated rates of aneusomy suggested that increased levels of chromosomal aberrations were associated with decreased telomere length. Moreover, multiple foci of HPIN were shown to have a heterogeneous overall reduction of telomere length. This reduction was more evident in the histologic regions of the prostate containing CaP. Such observations lend support to the hypothesis that telomere erosion may be a consistent feature of CaP oncogenesis and may also be associated with the generation of chromosomal instability that characterizes this malignancy.

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Acknowledgements

We thank Jana Karaskova, Ilan Braude, Jane Bayani and Lada Vorobyova for their technical expertise. We also thank Dr Lea Harrington and Dr Salomon Minkin for critical discussions and review. This research is supported by the Canadian Prostate Cancer Research Initiative.

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Authors and Affiliations

  1. Ontario Cancer Institute/Princess Margaret Hospital, The University Health Network, Toronto, M5G 2M9, Ontario, Canada

    Bisera Vukovic, Paul C Park, Jaudah Al-Maghrabi, Ben Beheshti & Jeremy Squire

  2. Department of Medical Biophysics, Faculty of Medicine, University of Toronto, The University Health Network, Toronto, M5G 2M9, Ontario, Canada

    Bisera Vukovic, Jaudah Al-Maghrabi & Jeremy Squire

  3. Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, The University Health Network, Toronto, M5G 2M9, Ontario, Canada

    Ben Beheshti, Joan Sweet, Andy Evans & Jeremy Squire

  4. Division of Pathology, Faculty of Medicine, University of Toronto, The University Health Network, Toronto, M5G 2M9, Ontario, Canada

    Joan Sweet & Andy Evans

  5. Divison of Urology, Faculty of Medicine, University of Toronto, The University Health Network, Toronto, M5G 2M9, Ontario, Canada

    John Trachtenberg

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  1. Bisera Vukovic
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Correspondence to Jeremy Squire.

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Vukovic, B., Park, P., Al-Maghrabi, J. et al. Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma. Oncogene 22, 1978–1987 (2003). https://doi.org/10.1038/sj.onc.1206227

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