Low expression of Ku70/80, but high expression of DNA-PKcs, predict good response to radiotherapy in early breast cancer

Abstract

Abstract. 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.

Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

“…Levels of DNA-PKcs in cancer cells before treatment (radiation or chemotherapy) has been compared to levels after treatment, and have shown mixed results. The expression of DNA-PKcs was noted to be directly proportional to a favorable response with radiation in esophageal and early breast cancer but not in nasopharyngeal cancer [36][37][38] . On the other hand, studies have revealed increased levels of DNA-PKcs and Ku proteins in residual tumors after radiation treatment, suggesting a means of survival and a marker of radioresistance in recurrent tumors [39] .…”