title: Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death.
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.
  
  
  CONCLUSIONS
  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 stratifi cation for individualized therapeutic and surveillance strategies.
authors.affiliation: 1Department of Pathology; 2James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; 4Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; Departments of 5Nutrition and 6Epidemiology, Harvard School of Public Health; and 7Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 8Department of Pathology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Heaphy
authors.forename: Ghil Suk
authors.initials: GS
authors.lastname: Yoon
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Peskoe
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Joshu
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Lee
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Kenfield
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
mesh_terms: D000368:Aged; D043171:Chromosomal Instability; D015331:Cohort Studies; D018572:Disease-Free Survival; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000503:physiopathology; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D017154:Stromal Cells / Q000378:metabolism / Q000648:ultrastructure*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure*