title: Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival.
abstract: To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we previously carried out cDNA microarray experiments on primary cervical cancer comparing patients with a complete response (CR) and those with no change (NC). Some of these genes had already been associated with the radiation response, such as x-ray repair cross-complementing 5 (XRCC5), which was found more in radioresistant tumors than in radiosensitive ones. The aim of this study was to confirm the possible roles of XRCC5 mRNA levels by a real-time polymerase chain reaction method in 20 cervical cancers, and Ku80 protein, which is the gene product of XRCC5, using a histopathologic method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 patients with cervical cancer. The levels of XRCC5 mRNA were 10(4.82) +/- 10(0.2) copies/microg total RNA in tumor tissues in the CR group (mean +/- standard deviation) and 10(4.95) +/- 10(0.32) copies/microg total RNA in those in the NC group. The levels of XRCC5 mRNA were not significantly different between the CR and NC groups. Histopathologic methods revealed 29.2% (26 of 89) of the patients to be Ku80-negative, with Ku80-positive findings in 70.8% (63 of 89). Of the Ku80-negative patients, 19 had CR, 3 had a partial response (PR), and 4 had NC. Of the Ku80-positive patients, 25 had CR, 22 had PR, and 16 had NC. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses (p = 0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive (p = 0.04). The results of this study suggest that a low expression of Ku80 protein leads to radiosensitivity in cervical cancer and that Ku80 might play a role in treatment outcome.
authors.affiliation: Department of Radiology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka, Japan. harima@takii.kmu.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Harima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sawada
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Kin
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ishihara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Sougawa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shikata
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000368:Aged; D034961:Antigens, Nuclear / Q000378:metabolism*; D001918:Brachytherapy; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen