Low expression of Ku70/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer.
The purpose was to study the prognostic and predictive roles of DNA protein kinase catalytic subunit (DNA-PKcs), Ku70/80 and p53 for the effect of radiotherapy in breast cancer patients. Protein expressions of Ku70/80, DNA-PKcs and p53 were examined using immunohistochemistry in tumours from 224 breast cancer patients, who were randomised to receive post-operative radiotherapy or adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil). One hundred and twenty-nine (60%) of the tumours had low expression of Ku70/80, 122 (57%) had low expression of DNA-PKcs and 65 (30%) had altered p53 expression. None of the proteins were indicative to the prognosis of local recurrence-free survival. Even though the expression of Ku70/80 and DNA-PKcs correlated well, they were not associated with treatment outcome in the same way. Low expression of Ku70/80 predicted good effect of radiotherapy (RR=0.31, 95% CI 0.13-0.76, p=0.01). In contrast, the greatest benefit of radiotherapy over chemotherapy was seen in patients with high DNA-PKcs expression (RR=0.25, 95% CI 0.07-0.84, p=0.02). Altered p53 expression predicted poor response to radiotherapy. We believe that the results reflect the different roles of DNA-PKcs and Ku70/80 in repair and cell death regulation after DNA damage. These differences could be of importance when developing drugs that target DNA repair.
Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Linköping University, Linköping, Sweden.
Karin
K
Söderlund Leifler
Siv
S
Queseth
Tommy
T
Fornander
Marie Stenmark
MS
Askmalm
D034961:Antigens, Nuclear / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen