Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma
Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma
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DOI：
10.1093/jnci/88.17.1228
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发表时间：
1996-09-04
期刊：
影响因子：
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通讯作者：
Soussi, T
中科院分区：
文献类型：
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作者：
Bourhis, J;Lubin, R;Soussi, T
背景：肿瘤抑制基因p53（又称TP53）的突变常导致合成半衰期长于正常的p53蛋白，利用免疫组化染色技术可检测到在肿瘤细胞核中积累的突变p53蛋白，在一些癌症患者中已检测到针对p53蛋白的血清抗体（p53- abs）。我们检测了80例头颈部鳞状细胞癌（HNSCC）患者的血清样本中p53-Abs的存在，并评估了这些抗体的存在与其他组织病理和临床特征之间的潜在关联。诊断时采集患者血清，治疗前取肿瘤活检标本，采用酶联免疫吸附法检测p53- abs，采用抗p53单克隆抗体DO7免疫组化检测肿瘤细胞核中p53蛋白的积累情况。患者的治疗包括单独放疗、初始化疗后放疗或手术和术后放疗，使用Kaplan-Meier法估计治疗开始时的无复发和总生存期；使用logrank统计进行生存比较，进行单因素和多因素分析以确定与生存相关的因素，报告的P值是双侧的，80例中有15例（18.8%）具有p53- abs， 73例可评估的活检标本中有43例（58.9%）的肿瘤细胞核显示强烈的p53免疫染色。患者的治疗方法和肿瘤细胞核中p53蛋白的积累与复发或死亡风险的增加无关。在单因素分析中，肿瘤晚期（>T1 [TNM分类]）和p53- abs的存在与死亡风险的增加显著相关（趋势P分别为0.007和0.002），而肿瘤晚期，大量区域淋巴结受损伤（>N1），p53-Abs的存在仅与复发风险增加相关（趋势P = 0.002, P = 0.02, P < 0.0001）。在多因素分析中，晚期肿瘤分期和p53-Abs的存在与复发（P趋势分别为0.04和0.003）和死亡（P趋势分别为0.03和0.03）的风险增加显著相关。随访2年时，未检测到p53-Abs时总生存率为63%(95%可信区间[CI] 47%-80%)，而检测到p53-Abs时总生存率为29% （95% CI为4%-54%）。未检测到p53- abs的2年无复发生存率为62% (95% CI = 49%-76%)，而检测到p53- abs的2年无复发生存率为13% （95% CI = 0%-31%）。结论和意义：血清中检测到p53- abs的HNSCC患者比例小于肿瘤细胞中p53蛋白积累的患者比例，p53- abs的存在与复发和死亡风险增加显著相关。
Background: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life, Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques, Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients, Purpose: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features, Methods: Serum was collected from each patient at the time of diagnosis, In addition, tumor biopsy specimens were obtained before the initiation of treatment, An enzyme-linked immunosorbent assay was used to detect p53-Abs, The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy, Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic, Univariate and multivariate analyses were conducted to identify factors associated with survival, Reported P values are two-sided, Fifteen (18.8%) of the 80 had p53-Abs, Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death, In univariate analyses, advanced tumor stage (>T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (>N1), and the presence of p53-Abs mere associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (P for trend = .04 and P = .003, respectively) and death (P for trend = .03 and P = .03, respectively), At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] 47%-80%) when no p53-Abs were detected compared with 29% (95% CI 4%-54%) when p53-Abs were detected, Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected, Conclusions aizd Implications: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein, The presence of p53-Abs is significantly associated with increased risks of relapse and death.