Organ-wide telomeric status in diseased and disease-free prostatic tissues

Christopher M. Heaphy, Trisha M. Fleet, Eric G. Treat, Sang Joon Lee, Anthony Y. Smith, Michael S. Davis, Jeffrey K. Griffith, Edgar G. Fischer, Marco Bisoffi

Research output: Contribution to journalArticle

Abstract

Background Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. Methods Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. Results Compared to TC in normal prostate samples (n=54; TC mean=0.98), tumor samples displayed telomere attrition (n=45; TC mean=0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n=73; TC mean=0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n=128; TC mean=1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. Conclusions Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer. Prostate 70: 1471-1479, 2010.

Original languageEnglish (US)
Pages (from-to)1471-1479
Number of pages9
JournalProstate
Volume70
Issue number13
DOIs
StatePublished - Sep 15 2010

Keywords

  • Benign prostatic hyperplasia
  • Field cancerization
  • Prostate cancer
  • Telomere alterations

ASJC Scopus subject areas

  • Oncology
  • Urology

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  • Cite this

    Heaphy, C. M., Fleet, T. M., Treat, E. G., Lee, S. J., Smith, A. Y., Davis, M. S., Griffith, J. K., Fischer, E. G., & Bisoffi, M. (2010). Organ-wide telomeric status in diseased and disease-free prostatic tissues. Prostate, 70(13), 1471-1479. https://doi.org/10.1002/pros.21182