Takada Yu, Someya Masanori, Matsumoto Yoshihisa, Satoh Masaaki, Nakata Kensei, Hori Masakazu, Saito Masato, Hirokawa Naoki, Tateoka Kunihiko, Teramoto Mizue, Saito Tsuyoshi, Hasegawa Tadashi, Sakata Koh-Ichi
Department of Radiology, School of Medicine, Sapporo Medical University, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.
Tokyo Institute of Technology, Research Laboratory for Nuclear Reactors, Tokyo, Japan.
Med Mol Morphol. 2016 Dec;49(4):210-216. doi: 10.1007/s00795-016-0136-5. Epub 2016 Feb 11.
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.
DNA双链断裂（DSB）是由电离辐射引起的严重损伤。非同源末端连接（NHEJ）是修复DSB的主要机制。对参与NHEJ的蛋白质（如Ku86和XRCC4（X射线修复交叉互补蛋白4））进行免疫组织化学分析，可能有助于预测肿瘤放射敏感性。我们研究了子宫颈癌活检标本中DSB相关蛋白的表达与40 Gy术前放疗的病理效果之间的关系。2000年至2011年期间，对119例子宫颈癌患者进行了治疗。通过检查子宫切除标本对术前放疗的病理效果进行分类。完全缓解（pCR）的患者总体5年生存率明显高于未达到pCR的患者（96.3%对76.9%，P = 0.02）。Ku86和XRCC4低表达患者的pCR率明显高于其他患者（47.4%对21.3%，P = 0.04）。逻辑回归分析也表明，Ku86和XRCC4低表达是pCR的重要预测指标（P = 0.03）。Ku86和XRCC4高表达的患者5年无转移率明显低于其他患者（79.3%对93.5%，P = 0.02）。参与NHEJ的蛋白质可能会影响子宫颈癌的放疗结果。
