title: Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.
abstract: DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan. horimasa@sapmed.ac.jp.
authors.forename: Masakazu
authors.identifier: http://orcid.org/0000-0002-6715-3891
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Someya
authors.affiliation: Tokyo Institute of Technology, Research Laboratory for Nuclear Reactors, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Gocho
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohnuma
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sugita
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
authors.forename: Koh-Ichi
authors.initials: KI
authors.lastname: Sakata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D000072200:Ku Autoantigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; C101467:XRCC4 protein, human; D051747:DNA-Activated Protein Kinase; D000072200:Ku Autoantigen
keywords: DNA-PKcs; Esophageal squamous cell carcinoma; Immunohistochemical staining; Ku86; Radiotherapy; XRCC4