p53 alterations are associated with improved prognosis in distal colonic carcinomas.
p53 alterations are associated with improved prognosis in distal colonic carcinomas.
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发表时间：
1997-08
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通讯作者：
Brett Dix;Derek Chen;Richard Parsons;Anthony K House;Barry Iacopetta
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作者：
Brett Dix;Derek Chen;Richard Parsons;Anthony K House;Barry Iacopetta
p53基因和p53蛋白的改变在广泛的人类恶性肿瘤中是常见的。在几种肿瘤类型中，p53基因突变和/或p53蛋白过表达与临床上更具侵袭性的表型相关，这是通过较差的患者生存率来判断的。这在结直肠癌中尚未得到明确证明。在此，我们报告了一个大系列的结直肠癌（n = 541）患者长期随访（平均87个月）的p53蛋白积累和基因突变的预后意义的结果。绝大多数患者（95%）未接受术后全身辅助治疗。单克隆抗体DO-7免疫组化检测p53聚集的发生率为30%，而PCR-单链构象多态性检测p53基因5-8外显子突变的发生率为36%。p53蛋白的积累与患者生存率的提高相关，与肿瘤分期或分级无关（风险比，0.66; 95%置信区间，0.47-0.93; P = 0.017）。根据肿瘤的位置观察到显著差异：起源于远端结肠的肿瘤显示出p53积聚的存在与患者生存率提高之间的强相关性（P = 0.003），但对于位于近端结肠的肿瘤则并非如此。Dukes'C期肿瘤，而不是B期，也显示p53积累和更好的结果之间的相关性（P = 0.013）。p53基因突变与生存率提高的趋势相关，特别是在远端肿瘤中。我们的研究结果表明，在某些肿瘤类型中，p53异常的存在可能与更好的预后相关。
Alterations of the p53 gene and the p53 protein are common in a wide spectrum of human malignancies. In several tumor types, p53 gene mutation and/or p53 protein overexpression correlate with a more clinically aggressive phenotype as judged by worse patient survival. This has not been clearly demonstrated to be the case in colorectal cancer. Herein, we report results of the prognostic significance of p53 protein accumulation and gene mutation in a large series of colorectal cancers (n = 541) with long patient follow-up (mean, 87 months). The large majority of patients (95%) received no postoperative systemic adjuvant therapy. The incidence of p53 accumulation detected by immunohistochemistry with the monoclonal antibody DO-7 was 30%, whereas the incidence of p53 gene mutation in exons 5-8 detected using PCR-single strand conformation polymorphism was 36%. Accumulation of p53 protein was associated with improved patient survival independent of tumor stage or grade (hazard ratio, 0.66; 95% confidence interval, 0.47-0.93; P = 0.017). A marked difference was observed depending on the location of the tumor: tumors originating in the distal colon showed a strong association between the presence of p53 accumulation and improved patient survival (P = 0.003), but this was not the case for those located in the proximal colon. Dukes' stage C tumors, but not stage B, also showed an association between p53 accumulation and better outcome (P = 0.013). Mutation of the p53 gene was associated with a trend toward improved survival, particularly in the distal tumors. Our results demonstrate that in some tumor types, the presence of p53 abnormalities can correlate with better prognosis.