title: Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy.
abstract: DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Yu
authors: Y
authors: Takada
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Masanori
authors: M
authors: Someya
authors: Tokyo Institute of Technology, Research Laboratory for Nuclear Reactors, Tokyo, Japan.
authors: Yoshihisa
authors: Y
authors: Matsumoto
authors: Division of Clinical Pathology, NTT Sapporo Hospital, Sapporo, Hokkaido, Japan.
authors: Masaaki
authors: M
authors: Satoh
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Kensei
authors: K
authors: Nakata
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Masakazu
authors: M
authors: Hori
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Masato
authors: M
authors: Saito
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Naoki
authors: N
authors: Hirokawa
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors: Kunihiko
authors: K
authors: Tateoka
authors: Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan.
authors: Mizue
authors: M
authors: Teramoto
authors: Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan.
authors: Tsuyoshi
authors: T
authors: Saito
authors: Department of Surgical Pathology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan.
authors: Tadashi
authors: T
authors: Hasegawa
authors: Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan. sakatako@sapmed.ac.jp.
authors: Koh-Ichi
authors: KI
authors: Sakata
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002452:Cell Count; D059766:DNA End-Joining Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000072200:Ku Autoantigen / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011300:Preoperative Care; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*
chemical_list: D004268:DNA-Binding Proteins; C101467:XRCC4 protein, human; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen
keywords: Immunohistochemical staining; Ku86; Radiotherapy; Uterine cervical cancer; XRCC4