The immunohistochemical expression of DNA-PKcs and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity

Björk‐Eriksson, Thomas; West, Catharine M L; Nilsson, Anders; Magnusson, Bengt; Svensson, Marie; Karlsson, Ewa; Slevin, Nicholas J; Lewensohn, Rolf; Mercke, Claes

doi:10.1016/s0360-3016(99)00268-0

Cited by 34 publications

(24 citation statements)

References 26 publications

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“…A recent study suggests that the DNA-PK complex is upregulated in cervical carcinoma cells surviving radiotherapy, indicating that upregulation of DNA-PK may be involved in radioresistance (39). Two studies have found no significant correlation between expression of the DNA-PK subunits and radiosensitivity (31,40). In the current study, we found that high, rather than low expression, of DNA-PKcs was related to a good response to radiotherapy.…”

Section: Discussionsupporting

confidence: 49%

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

Leifler

Queseth²,

Fornander³

et al. 2010

Int J Oncol

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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.

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Section: Discussionsupporting

confidence: 49%

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

Leifler

Queseth²,

Fornander³

et al. 2010

Int J Oncol

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“…There are clinical studies on DNA-PK and outcome of RT on other tumour sites with diverging results. In head and neck cancer there are reports of no correlation between expression of DNA-PKcs and the subunits Ku70/Ku86 and in vitro radiosensitivity of explanted tumours (Björk-Eriksson et al, 1999), while in another study tumours with high levels of Ku86 displayed better locoregional control after RT as compared with tumours expressing low levels of Ku86 (Friesland et al, 2003). In a study of patients with rectal carcinoma treated with preoperative RT, low levels of Ku70 immunostaining was related to radiosensitivity (Komuro et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB–IIA of cervical cancer

et al. 2006

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The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB -IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P ¼ 0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.

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“…A correlation between Ku80 and DNA-PKcs expression has been reported in patients with colorectal cancer and head and neck cancer. 20,29 The promoter regions of both Ku80 and DNA-PKcs contain consensus SP1 recognition elements; thus, DNA-PKcs and Ku80 may be regulated transcriptionally by SP1. A connection also may exist between the levels of DNA-PKcs and ATM.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of ataxia‐telangiectasia mutated, DNA‐dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86‐kD subunit expression in patients with nonsmall cell lung cancer

Xing

Vaporciyan

et al. 2008

Cancer

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BACKGROUND.The double‐strand break (DSB) repair capacity has been implicated in the survival of patients in several cancer types. However, little is known about the prognostic importance of the key DSB repair genes—ataxia‐telangiectasia mutated (ATM), DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs), and the Ku heterodimeric regulatory complex 86‐kD subunit (Ku80)—in nonsmall cell lung cancer (NSCLC). To address this issue, the authors determined the messenger RNA (mRNA) expression of these genes in patients NSCLC and assessed their prognostic relevance.METHODS.mRNA expression levels of ATM, DNA‐PKcs, and Ku80 were measured in tumor and adjacent normal tissues from 140 patients with NSCLC by using quantitative real‐time polymerase chain reaction analysis. Then, a Cox proportional hazards regression model and Kaplan‐Meier plots were used to evaluate the association between the tumor:normal (T/N) expression ratios of the 3 genes and the overall survival rate and duration in patients with NSCLC.RESULTS.mRNA expression of ATM and DNA‐PKcs, but not of Ku80, was significantly higher in tumor tissues than in adjacent normal tissues (P = .003 and P < .001, respectively). The high T/N expression ratios of ATM and DNA‐PKcs were associated significantly with a 1.82‐fold increased risk of death (95% confidence interval, 1.05–2.70) and a 2.13‐fold increased risk of death (95% confidence interval, 1.21–3.76), respectively. However, no significant association with risk was observed for Ku80. Kaplan‐Meier analyses revealed that patients with high T/N expression ratios of ATM or DNA‐PKcs had notably shorter median survival than patients with low ratios.CONCLUSIONS.The current findings suggested that the T/N expression ratios of ATM and DNA‐PKcs may be useful for identifying NSCLC patients with a poor prognosis who may benefit from more aggressive therapy. Cancer 2008. ©2008 American Cancer Society.

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The immunohistochemical expression of DNA-PKcs and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity

Cited by 34 publications

References 26 publications

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

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

Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB–IIA of cervical cancer

Prognostic significance of ataxia‐telangiectasia mutated, DNA‐dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86‐kD subunit expression in patients with nonsmall cell lung cancer

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