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The Significance of Ku70 Expression in Patients with Nasopharyngeal Carcinoma  

Song Si Yeol (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
Lee Sang-wook (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
Yu Eunsil (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Cho Kyung-Ja (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Park Jin-hong (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
Kim Sang Yoon (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Nam Soon Yuhl (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Lee Bong-Jae (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Kim Sung Bae (Department of Otorhinolaryngology, University of Ulsan College of Medicine, Asan Medical Center)
Choi Seung-Ho (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Ahn Seung Do (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
Shin Seong Soo (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
Choi Eun Kyung (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
Publication Information
Radiation Oncology Journal / v.23, no.1, 2005 , pp. 1-8 More about this Journal
Abstract
Purpose : The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-PKcs, influence the response to radiotherapy (RT) and outcome of treatment of non-disseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Materials and Methods : Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The over-expression of Ku70 or DNA-PKcs groups Included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were peformed to determine the prognostic factors that influenced locoregional control of NPC. Results : The five-year locoregional control rate was significantly higher in the low Ku70 group (Ku(-)) (85%) than in the high Ku70 group (Ku(+)) (42%) (p=0.0042). However, there were no differences in the metastases-free survival rates between the two groups (Ku70 (+), 82%; Ku70 (-), 78%; p=0.8672). Univariate analysis indicated that the over-expression of Ku70 surpassed other well-known predictive clinocopathologic parameters as an Independent prognostic factor for locoregionai control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an over-expression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Conclusion : Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with non-disseminated NPC.
Keywords
Chemotherapy; DNA-PKcs; Immunohistochemistry; Nasopahryngeal carcinoma; Radiotherapy; Ku70;
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1 Lee AW, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys 1992;23:261-270   DOI   PUBMED   ScienceOn
2 Featherstone C, Jackson SP. Ku, a DNA repair protein with multiple cellular functions? Mutat Res 1999;434:3-15   DOI   ScienceOn
3 Jeggo PA. DNA-PK: at the cross-roads of biochemistry and genetics. Mutat Res 1997;384:1-14   DOI   PUBMED   ScienceOn
4 Lieber MR, Grawunder U, Wu X, et al. Tying loose ends: roles of Ku and DNA-dependent protein kinase in the repair of double-strand breaks. Curr Opin Genet Dev 1997;7:99-104   DOI   ScienceOn
5 Muller C, Calsou P, Frit P, et al. Regulation of the DNAdependent protein kinase (DNA-PK) activity in eukaryotic cells. Biochimie 1999;81:117-125   DOI   ScienceOn
6 Komuro Y, Watanabe T, Hosoi Y, et al. The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer 2002;95:1199-1205   DOI   PUBMED   ScienceOn
7 Polischouk AG, Cedervall B, Ljungquist S, et al. DNA double-strand break repair, DNA-PK, and DNA ligases in two human squamous carcinoma cell lines with different radiosen sitivity. Int J Radiat Oncol Biol Phys 1999;43:191-198   DOI   ScienceOn
8 Lim JH, Kim GE, Keum KC, et al. Parotid Gland Sparing Radiotherapy Technique Using 3-D Conformal Radiotherpy for Nasopharyngeal Carcinoma. Korean Soc Ther Radiol 2000;18:1-10
9 Kim GE. Does the Addition of Adjuvant Chemotherapy to Concurrent Chemoradiotherapy Improve the Survival of Patients with Locally Advanced Nasopharyngeal Cancer? Cancer Res Treat 2003;35:369-372   DOI
10 van Heemst D, Brugmans L, Verkaik NS, et al. Endjoining of blunt DNA double-strand breaks in mammalian fibroblasts is precise and requires DNA-PK and XRCC4. DNA Repair (Amst) 2004;3:43-50   DOI   ScienceOn
11 Kwong DL, Nicholls J, Wei WI, et al. The time course of histologic remission after treatment of patients with nasopharyngeal carcinoma. Cancer 1999;85:1446-1453   DOI   PUBMED   ScienceOn
12 Yu KH TP, Lee WY, Leung SF, Choi PH, Johnson PJ. Patterns of early treatment failure in non-metastatic nasopharyngeal carcinoma: a study based on CT scanning. Clin Oncol 1994;6:167-171   DOI   ScienceOn
13 Jaulerry C, Dubray B, Brunin F, et al. Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study. Int J Radiat Oncol Biol Phys 1995;33:271-279   DOI   ScienceOn
14 Wilson CR, Davidson SE, Margison GP, et al. Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer 2000;83:1702-1706   DOI   ScienceOn
15 Greene FL PD, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M. AJCC cancer staging manual. 6th ed. Chicago: Springer; 1997
16 Mimori T, Akizuki M, Yamagata H, et al. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J Clin Invest 1981;68:611-620   DOI
17 Korabiowska M, Bauer H, Quentin T, et al. Application of new in situ hybridization probes for Ku70 and Ku80 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemical analysis. Hum Pathol 2004;35:210-216   DOI   ScienceOn
18 Perez CA, Devineni VR, Marcial-Vega V, et al. Carcinoma of the nasopharynx: factors affecting prognosis. Int J Radiat Oncol Biol Phys 1992;23:271-280   DOI   ScienceOn
19 Cooper JS, del Rowe J, Newall J. Regional Stage IV carcinoma of the nasopharynx treated by aggressive radiotherapy. Int J Radiat Oncol Biol Phys 1983;9:1737-1745   DOI   PUBMED   ScienceOn
20 Grandi C, Boracchi P, Mezzanotte G, et al. Analysis of prognostic factors and proposal of a new classification for nasopharyngeal cancer. Head Neck 1990;12:31-40   DOI   ScienceOn
21 Bjork-Eriksson T, West C, Nilsson A, et al. The immunohistochemical expression of DNA-PKCS and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity. Int J Radiat Oncol Biol Phys 1999;45:1005-1010   DOI   ScienceOn
22 Friesland S, Kanter-Lewensohn L, Tell R, et al. Expression of Ku86 confers favorable outcome of tonsillar carcinoma treated with radiotherapy. Head Neck 2003;25:313-321   DOI   ScienceOn
23 Anderson CW. DNA damage and the DNA-activated protein kinase. Trends Biochem Sci 1993;18:433-437   DOI   PUBMED   ScienceOn
24 Lustig AJ. The Kudos of non-homologous end-joining. Nat Genet 1999;23:130-131   DOI   PUBMED   ScienceOn
25 Sham JS, Choy D. Prognostic factors of nasopharyngeal carcinoma: a review of 759 patients. Br J Radiol 1990;63:51-58.   DOI   ScienceOn
26 Jin S, Kharbanda S, Mayer B, et al. Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit. J Biol Chem 1997;272:24763-24766   DOI   ScienceOn
27 Yoko H SS, Yoshitaka M, Kiyonori K, et al. Expression of Ku80 in Cervical Cancer Correlates With Response to Radiotherapy and Survival. Am J Clin Oncol 2003;26:e80-e85   DOI   ScienceOn
28 Zhao HJ, Hosoi Y, Miyachi H, et al. DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines. Clin Cancer Res 2000;6:1073-1078
29 Flores AD, Dickson RI, Riding K, et al. Cancer of the nasopharynx in British Columbia. Am J Clin Oncol 1986;9:281-291   DOI   PUBMED
30 Lee AW, Law SC, Foo W, et al. Nasopharyngeal carcinoma: local control by megavoltage irradiation. Br J Radiol 1993;66:528-536   DOI   ScienceOn
31 Sirzen F, Nilsson A, Zhivotovsky B, et al. DNA-dependent protein kinase content and activity in lung carcinoma cell lines: correlation with intrinsic radiosensitivity. Eur J Cancer 1999;35:111-116   DOI   ScienceOn
32 Kasten U, Plottner N, Johansen J, et al. Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts. Br J Cancer 1999;79:1037-1041   DOI   PUBMED