DNA-PKcs Expression Is a Predictor of Biochemical Recurrence After Permanent Iodine 125 Interstitial Brachytherapy for Prostate Cancer.
Predictive factors for biochemical recurrence (BCR) in localized prostate cancer (PCa) after brachytherapy are insufficient to date. Cellular radiosensitivity depends on DNA double-strand breaks, mainly repaired by the nonhomologous end-joining (NHEJ) system. We analyzed whether the expression of NHEJ proteins can predict BCR in patients treated by brachytherapy for localized PCa.



From 983 PCa cases treated by brachytherapy between March 2000 and March 2012, 167 patients with available biopsy material suitable for in situ analysis were included in the study. The median follow-up time was 47 months. Twenty-nine patients experienced BCR. All slides were reviewed to reassess the Gleason score. Expression of the key NHEJ proteins DNA-PKcs, Ku70, and Ku80, and the proliferation marker Ki67, was studied by immunohistochemistry performed on tissue microarrays.



The Gleason scores after review (P=.06) tended to be associated with BCR when compared with the score initially reported (P=.74). Both the clinical stage (P=.02) and the pretreatment prostate-specific antigen level (P=.01) were associated with biochemical failure. Whereas the expression of Ku80 and Ki67 were not predictive of relapse, positive DNA-PKcs nuclear staining (P=.003) and higher Ku70 expression (P=.05) were associated with BCR. On multivariate analysis, among pretreatment variables, only DNA-PKcs (P=.03) and clinical stage (P=.02) remained predictive of recurrence. None of the patients without palpable PCa and negative DNA-PKcs expression experienced biochemical failure, compared with 32% of men with palpable and positive DNA-PKcs staining that recurred.



Our results suggest that DNA-PKcs could be a predictive marker of BCR after brachytherapy, and this might be a useful tool for optimizing the choice of treatment in low-risk PCa patients.
Department of Pathology, INSERM UMR1069, CHU/Université de Tours, Tours, France; Department of Radiation Oncology, CHU/Université de Poitiers, Poitiers, France.
Sarah
S
Molina
Department of Radiation Oncology, CHU/Université de Poitiers, Poitiers, France.
Stéphane
S
Guerif
Department of Radiation Oncology, CHU/Université de Poitiers, Poitiers, France.
Alexandre
A
Garcia
Department of Pathology, CHU/Université de Poitiers, Poitiers, France.
Céline
C
Debiais
Department of Urology, CHU/Université de Poitiers, Poitiers, France.
Jacques
J
Irani
Department of Pathology, INSERM UMR1069, CHU/Université de Tours, Tours, France. Electronic address: gaelle.fromont-hankard@univ-tours.fr.
Gaëlle
G
Fromont
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001918:Brachytherapy / Q000706:statistics & numerical data*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D005602:France / Q000453:epidemiology; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000378:metabolism* / Q000517:prevention & control; D009687:Nuclear Proteins / Q000378:metabolism*; D015995:Prevalence; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D009687:Nuclear Proteins; D019275:Radiopharmaceuticals; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human