DNA-PKcs expression predicts response to radiotherapy in prostate cancer

Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1179-85. doi: 10.1016/j.ijrobp.2012.02.014. Epub 2012 Apr 9.


Purpose: Double-strand breaks, the most lethal DNA lesions induced by ionizing radiation, are mainly repaired by the nonhomologous end-joining system. The expression of the nonhomologous end-joining pathway has never been studied in prostate cancer, and its prognostic value for patients undergoing radiotherapy remains unknown.

Methods: Pretreatment biopsies from 238 patients treated with exclusive external beam radiotherapy for localized prostate cancer with ≥ 2 years of follow-up were reviewed to reassess the Gleason score. Of these 238 cases, 179 were suitable for in situ analysis and were included in the tissue microarrays. Expression of the nonhomologous end-joining proteins Ku70, Ku80, DNA-dependent protein kinase, catalytic subunits (DNA-PKcs), and X-ray repair cross complementing 4-like factor was studied by immunohistochemistry, together with the proliferation marker Ki67.

Results: The predictive value of the Gleason score for biochemical relapse (using the Phoenix criteria) was markedly improved after review (P<.0001) compared with the initial score (P=.003). The clinical stage, pretreatment prostate-specific antigen level, and perineural invasion status were also associated with progression-free survival (P=.005, P<.0001, and P=.03, respectively). High proliferation (>4%) tends to be associated with biochemical recurrence; however, the difference did not reach statistical significance (P=.06). Although the expression of Ku70, Ku80, and X-ray repair cross complementing 4-like factor was not predictive of relapse, positive DNA-PKcs nuclear staining was closely associated with biochemical recurrence (P=.0002). On multivariate analysis, only the Gleason score, prostate-specific antigen level, and DNA-PKcs status remained predictive of recurrence (P=.003, P=.002, and P=.01, respectively).

Conclusions: The results of the present study highly suggest that DNA-PKcs could be a predictive marker of recurrence after radiotherapy, independently of the classic prognostic markers, including the Gleason score modified after review.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear / metabolism
  • Cell Nucleus / metabolism
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair / genetics
  • DNA Repair Enzymes / metabolism
  • DNA-Activated Protein Kinase / metabolism*
  • DNA-Binding Proteins / metabolism
  • Disease-Free Survival
  • Humans
  • Ki-67 Antigen / metabolism
  • Ku Autoantigen
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Neoplasm Recurrence, Local*
  • Predictive Value of Tests
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Tissue Array Analysis / methods


  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • NHEJ1 protein, human
  • Neoplasm Proteins
  • DNA-Activated Protein Kinase
  • Prostate-Specific Antigen
  • Xrcc6 protein, human
  • Ku Autoantigen
  • DNA Repair Enzymes