Hayashi Jyunichi, Sakata Koh-Ichi, Someya Masanori, Matsumoto Yoshihisa, Satoh Masaaki, Nakata Kensei, Hori Masakazu, Takagi Masaru, Kondoh Atsushi, Himi Tetsuo, Hareyama Masato
Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido.
Oncol Lett. 2012 Jul;4(1):151-155. doi: 10.3892/ol.2012.674. Epub 2012 Apr 5.
DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10-20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer.
DNA双链断裂（DSB）是电离辐射诱导产生的最严重的损伤形式之一。非同源末端连接（NHEJ）是DNA双链断裂修复的关键机制。对参与NHEJ的蛋白质进行免疫组织化学分析可能具有作为肿瘤放射敏感性预测检测方法的潜力。我们研究了下咽癌活检标本中参与DNA双链断裂的蛋白质表达与放化疗结果之间的相关性。2002年3月至2009年12月期间，对57例未经治疗的下咽鳞状细胞癌患者进行了治疗。大多数患者（75%）患有III期或IV期疾病。化疗方案为顺铂加5氟尿嘧啶或S-1。通常对原发肿瘤和区域淋巴结给予50 Gy的肿瘤剂量。在50 Gy后，通常对原发肿瘤缩小照射野追加10 - 20 Gy的剂量。I期患者的5年无病生存率为100%，II期为90%，III期为64%，IV期为50%。在I - III期，Ku70或XRCC4表达较低的患者往往具有更好的局部区域控制。这些结果表明，Ku70或XRCC4表达较低可能与较高的放射敏感性相关。两名患者仅发生远处转移，其中一名患者Ku70表达为0%，另一名患者Ku86表达为0%。Ku70或Ku86表达缺失表明DNA-PK活性较低。由于Ku表达低导致的低DNA-PK活性可能导致癌细胞的基因改变，从而导致更高的远处转移倾向。这一发现表明，参与NHEJ的蛋白质可能对下咽癌放化疗的治疗结果产生影响。
