Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy

• Published in: Medical molecular morphology 2017-03, Vol.50 (1), p.25-33
• Main Authors: Hori, Masakazu, Someya, Masanori, Matsumoto, Yoshihisa, Nakata, Kensei, Kitagawa, Mio, Hasegawa, Tomokazu, Tsuchiya, Takaaki, Fukushima, Yuki, Gocho, Toshio, Sato, Yasushi, Ohnuma, Hiroyuki, Kato, Junji, Sugita, Shintaro, Hasegawa, Tadashi, Sakata, Koh-Ichi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anatomy; Deoxyribonucleic acid; DNA; DNA-Activated Protein Kinase - metabolism; DNA-Binding Proteins - metabolism; Drug therapy; Esophageal cancer; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - radiotherapy; Female; Gene expression; Humans; Ku Autoantigen - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Molecular Medicine; Multivariate Analysis; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Original Paper; Pathology; Proportional Hazards Models; Radiology; Treatment Outcome
• ISSN: 1860-1480; 1860-1499
• DOI: 10.1007/s00795-016-0144-5

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.