Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma.
OBJECTIVE
The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-protein kinase catalytic subunit (DNA-PKcs), influence the response to radiotherapy (RT) and outcome of treatment of nondisseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT.


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 overexpression 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 performed to determine the prognostic factors that influenced locoregional control of NPC.


RESULTS
The 5-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 2 groups (Ku70+, 82%; Ku70- 78%; p = 0.8672). Univariate analysis indicated that the overexpression of Ku70 surpassed other well-known predictive clinicopathologic parameters as an independent prognostic factor for locoregional control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an overexpression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome.


CONCLUSIONS
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 nondisseminated NPC.
Lee
Sang-Wook
SW
Department of Radiation Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
Cho
Kyung-Ja
KJ
Park
Jin-Hong
JH
Kim
Sang Yoon
SY
Nam
Soon Yuhl
SY
Lee
Bong-Jae
BJ
Kim
Sung-Bae
SB
Choi
Seung-Ho
SH
Kim
Jong Hoon
JH
Ahn
Seung Do
SD
Shin
Seong Soo
SS
Choi
Eun Kyung
EK
Yu
Eunsil
E
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D034961:Antigens, Nuclear / Q000378:metabolism*; D003131:Combined Modality Therapy; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011836:Radiation Tolerance; D015996:Survival Rate; D016896:Treatment Outcome
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen