The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma.
BACKGROUND
Preoperative radiotherapy reduces the rate of local recurrence and improves the chance of survival in patients with resectable, advanced rectal carcinoma. However, because not all tumors respond similarly to radiation, sorting out suitable patients is required to irradiate tumors rationally. The authors examined the possible role of Ku protein in determining tumor radiosensitivity and disease free survival in patients with rectal carcinoma.


METHODS
The authors studied 96 patients with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells that were stained positive for Ku protein was evaluated by immunohistochemistry. The expression pattern of Ku protein was examined for an association between tumor radiosensitivity (which was determined according to T classification downstaging, complete pathologic response, or Response Evaluation Criteria in Solid Tumors) and disease free survival.


RESULTS
There was a high degree of correlation between the percentage of cells that expressed the 70-kDa Ku protein (Ku70) and the 86-kDa Ku protein (Ku86) in the tumor sections (correlation coefficient = 0.85; P < 0.001). The expression pattern of Ku protein was correlated not only with tumor radiosensitivity but also with disease free survival. Pathologic TMN classification, histopathologic grade, and Ku70 expression were significant prognostic variables for disease free survival in a multivariate analysis (P = 0.0031, P = 0.030, and P = 0.023, respectively).


CONCLUSIONS
Ku70 and Ku86 raise the predictive possibility of tumor radiosensitivity. Ku may be a useful parameter for selecting patients with rectal carcinoma for preoperative radiotherapy.
Komuro
Yasuhiro
Y
Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Japan. komuro@kt.rim.or.jp
Watanabe
Toshiaki
T
Hosoi
Yoshio
Y
Matsumoto
Yoshihisa
Y
Nakagawa
Keiichi
K
Tsuno
Nelson
N
Kazama
Shinsuke
S
Kitayama
Joji
J
Suzuki
Norio
N
Nagawa
Hirokazu
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D011836:Radiation Tolerance / Q000502:physiology*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen