Okubo R, Masuda H, Nemoto N
Department of Functional Physiology, Nihon University School of Medicine, Nerima-ku, Tokyo 179-0072, Japan.
Oncol Rep. 2001 May-Jun;8(3):509-14. doi: 10.3892/or.8.3.509.
There has been few reports describing that the prognostic significance of p53 alteration in colorectal tumors depended on the site of origin. Therefore, in this study, we examined whether there is a valid association between the p53 alterations and the prognosis of colorectal cancer patients, especially distal colorectal cancer cases. Tumor samples were collected from 110 patients resected for colorectal cancer between 1989 and 1997. The entire coding region of the p53 gene was analyzed by automated direct sequencing. In addition, the DO-7 monoclonal antibody was used in the immunohistochemical (IHC) assessments. By the Cox univariate analyses in all tumors, Dukes' stage, lymph node metastasis, liver metastasis, p53 mutation and p53 protein overexpression were significant predictors of survival. The cases without p53 mutation showed significantly improved prognosis compared to the cases with p53 mutation (p = 0.0085). In distal tumors, Dukes' stage, liver metastasis, p53 mutation and p53 protein overexpression were significant predictors of survival. Multivariate analysis of all tumors, p53 mutation and liver metastasis were independent indicators of poor survival (p = 0.0223 for p53 mutation, p = 0.0254 for liver metastasis). Also in distal tumors, p53 mutation was an independent indicator (p = 0.0011). Furthermore, the relative risk associated with p53 mutation in distal tumors was much higher than that in all tumors (8.260 vs. 1.796). However, p53 protein overexpression was not an independent indicator of survival in all tumors as well as distal tumors (p = 0.1918 in all tumors, p = 0.0607 in distal tumors). In proximal tumors, p53 mutation was not an independent indicator (p = 0.6673). We think that p53 mutation is a very useful prognostic indicator when distal colorectal cancers are considered.
鲜有报道描述结直肠肿瘤中p53改变的预后意义取决于肿瘤的起源部位。因此，在本研究中，我们探讨了p53改变与结直肠癌患者预后之间是否存在有效关联，尤其是远端结直肠癌病例。收集了1989年至1997年间因结直肠癌接受手术切除的110例患者的肿瘤样本。通过自动直接测序分析p53基因的整个编码区。此外，DO-7单克隆抗体用于免疫组织化学（IHC）评估。在所有肿瘤的Cox单因素分析中，Dukes分期、淋巴结转移、肝转移、p53突变和p53蛋白过表达是生存的显著预测因素。与p53突变的病例相比，无p53突变的病例预后显著改善（p = 0.0085）。在远端肿瘤中，Dukes分期、肝转移、p53突变和p53蛋白过表达是生存的显著预测因素。对所有肿瘤进行多因素分析，p53突变和肝转移是生存不良的独立指标（p53突变p = 0.0223，肝转移p = 0.0254）。在远端肿瘤中，p53突变也是一个独立指标（p = 0.0011）。此外，远端肿瘤中与p53突变相关的相对风险远高于所有肿瘤中的相对风险（8.260对1.796）。然而，p53蛋白过表达在所有肿瘤以及远端肿瘤中均不是生存的独立指标（所有肿瘤中p = 0.1918，远端肿瘤中p = 0.0607）。在近端肿瘤中，p53突变不是独立指标（p = 0.6673）。我们认为，当考虑远端结直肠癌时，p53突变是一个非常有用的预后指标。
