Komuro Yasuhiro, Watanabe Toshiaki, Tsurita Giichiro, Muto Tetsuichiro, Nagawa Hirokazu
Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Hepatogastroenterology. 2005 May-Jun;52(63):666-71.
BACKGROUND/AIMS: The local recurrence ratio following surgery alone is higher in patients with rectal cancer than in those with colon cancer. Preoperative radiotherapy reduces the rate of local recurrence and improves the chances of survival in patients with resectable advanced rectal carcinoma. Identification of predictive indicators of radiosensitivity is useful in selecting patients best suited for preoperative radiotherapy and thus helps to avoid unnecessary preoperative treatment. We investigated whether the combination of Ku, p53, p21, and p16 predicted tumor radiosensitivity.
We studied 96 cases with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, all immunoreactive nuclei of cells stained positive for Ku, p53, p21, and p16 were evaluated by immunohistochemistry. The expression of p53, p21 and p16 in more than 5% of tumor cells were defined as positive, whereas both Ku70 and Ku86 protein in more than 70% of such cells were defined as Ku positive. The expression patterns of Ku, p53, p21, and p16 were examined for association with tumor radiosensitivity, which was determined according to the criteria of histopathologic assessment of radiotherapy effects.
Univariate analysis showed a correlation between the expression patterns of Ku, p53, p21, and p16 and tumor radiosensitivity, while multivariate analysis showed that the expression pattern of Ku and p16 significantly correlated with tumor radiosensitivity. The combination of Ku and p16, or Ku, p53, p21 and p16 was therefore a good predictive marker for tumor radiosensitivity.
These findings tend to support the hypothesis that the combination of Ku, p53, p21, and p16 expression after radiotherapy can act as a marker for radiosensitivity. Further investigation is needed, as the number of cases in this study was limited.
背景/目的：直肠癌患者单纯手术后的局部复发率高于结肠癌患者。术前放疗可降低局部复发率，并提高可切除的晚期直肠癌患者的生存几率。识别放射敏感性的预测指标有助于选择最适合术前放疗的患者，从而避免不必要的术前治疗。我们研究了Ku、p53、p21和p16的联合检测是否可预测肿瘤放射敏感性。
我们研究了96例晚期直肠癌患者。在放疗前肿瘤样本的活检标本中，通过免疫组织化学评估所有Ku、p53、p21和p16染色阳性细胞的免疫反应性细胞核。肿瘤细胞中超过5%表达p53、p21和p16被定义为阳性，而超过70%的此类细胞中Ku70和Ku86蛋白均表达则被定义为Ku阳性。根据放疗效果的组织病理学评估标准确定肿瘤放射敏感性，并检测Ku、p53、p21和p16的表达模式与肿瘤放射敏感性之间的关联。
单因素分析显示Ku、p53、p21和p16的表达模式与肿瘤放射敏感性之间存在相关性，而多因素分析显示Ku和p16的表达模式与肿瘤放射敏感性显著相关。因此，Ku和p16的联合检测，或Ku、p53、p21和p16的联合检测是肿瘤放射敏感性的良好预测指标。
这些发现倾向于支持放疗后Ku、p53、p21和p16表达的联合检测可作为放射敏感性标志物的假说。由于本研究的病例数有限，需要进一步研究。
