Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

Authors:
  • CHChristopher M. Heaphy
    Christopher M. Heaphy
  • GYGhil Suk Yoon
    Ghil Suk Yoon
  • SPSarah B. Peskoe
    Sarah B. Peskoe
  • CJCorinne E. Joshu
    Corinne E. Joshu
  • TLThomas K. Lee
    Thomas K. Lee
  • EGEdward Giovannucci
    Edward Giovannucci
  • LMLorelei A. Mucci
    Lorelei A. Mucci
  • SKStacey A. Kenfield
    Stacey A. Kenfield
  • MSMeir J. Stampfer
    Meir J. Stampfer
  • JHJessica L. Hicks
    Jessica L. Hicks
  • AMAngelo M. De Marzo
    Angelo M. De Marzo
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Abstract
Current prognostic indicators are imperfect predictors of outcome in men with clinically localized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer–associated stromal (CAS) cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies. Significance: In this prospective study, the combination of more variable telomere length among cancer cells and shorter telomere length in CAS cells was strongly associated with progression to metastasis and prostate cancer death, pointing to the translational potential for prognostication and risk stratification for individualized therapeutic and surveillance strategies. Cancer Discov; 3(10); 1130–41. ©2013 AACR. See related commentary by Shay, p. 1096 This article is highlighted in the In This Issue feature, p. 1083

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