Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer
Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer
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DOI：
10.1093/jnci/89.5.381
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发表时间：
1997-03-05
影响因子：
10.3
通讯作者：
Dalmau, J
中科院分区：
文献类型：
--
作者：
Rosenfeld, MR;Malats, N;Dalmau, J
背景：一些癌症患者会产生针对p53肿瘤抑制蛋白的抗体。这些抗体在血清中的存在与肿瘤突变型p53的表达相关，在一些研究中与较差的存活率相关。目的：本研究的目的是确定新诊断的小细胞肺癌（SCLC）患者血清中抗p53抗体的患病率，并评估血清中这些抗体存在的临床相关性，特别是它们与肿瘤治疗反应和患者生存率的关系。研究方法：在这项前瞻性研究中，从1991年10月至1994年6月在西班牙巴塞罗那的四家医院中的任何一家接受铂类或阿霉素化疗的170名诊断为SCLC的患者中获得血清。来自血库供体的正常人血清（n = 50）用作对照。使用纯化的重组p53蛋白通过蛋白质印迹分析确定抗p53抗体的存在。截至1996年1月，96.5%的患者在研究中接受了治疗和观察，中位随访时间为33.5个月。通过Kaplan-Meier方法估计存活率。进行考克斯比例风险回归和非条件Logistic回归分析。所有P值均来自双侧检验。结果：170例患者中有27例（16%）血清中检测到抗p53抗体。来自正常个体的50个血清样品中没有一个含有抗p53抗体。治疗前临床特征的分析表明，体重减轻小于5%（P = 0.025），血清乳酸脱氢酶（LDH）水平小于450 U/L（P = 0.002），并且疾病分期有限（即，肿瘤局限于一侧半胸，允许局部和区域淋巴结肿瘤细胞阳性和/或同侧胸腔积液）血清抗p53抗体的存在与临床特征如年龄无关（P = .622），功能状态（P = 1.0），疾病分期（P = .634），治疗完全缓解（P = 0.572）和生存率（P = .492）或任何实验室参数，包括SCLC中已知的预后因素，如血清钠或LDH浓度（P值分别为.731和.246）。结论和影响：新诊断的SCLC患者血清中抗p53抗体的存在与任何临床特征或预后标志物无关，这表明在这种情况下，抗p53抗体的测量不是有用的预后标志物。
Background: Some patients with cancer develop antibodies against the p53 tumor suppressor protein. The presence of these antibodies in serum has been associated with the expression of mutant p53 by the tumor and in some studies with a poorer survival. Purpose: The goals of this study were to determine the prevalence of anti-p53 antibodies in the serum of patients with newly diagnosed small-cell lung cancer (SCLC) and to assess the clinical relevance of the presence of these antibodies in the serum, particularly their relationship with tumor response to treatment and with patient survival. Methods: In this prospective study, serum was obtained from 170 patients at the time of diagnosis of SCLC who were to subsequently receive platinum- or doxorubicin-based chemotherapy at any one of four hospitals in Barcelona, Spain, from October 1991 through June 1994. Normal human sera from blood bank donors (n = 50) served as controls. The presence of anti-p53 antibodies was determined by western blot analysis with the use of purified recombinant p53 protein. As of January 1996, 96.5% of the patients had been treated and observed in the study, for a median follow-up time of 33.5 months. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression and unconditional logistic regression analyses were conducted. All P values resulted from two-sided tests, Results: Anti-p53 antibodies were detected in the serum of 27 (16%) of the 170 patients studied. None of 50 serum samples from normal individuals contained anti-p53 antibodies, Analysis of pretreatment clinical characteristics demonstrated that a weight loss of less than 5% (P = .025), a serum lactic acid dehydrogenase (LDH) level of less than 450 U/L (P = .002), and limited stage disease (i.e., tumor confined to one hemithorax, with local and regional lymph node positivity for tumor cells and/or ipsilateral pleural effusion allowed) (P < .001) were associated with a statistically significant complete response to therapy, The presence of serum anti-p53 antibodies was not associated with clinical characteristics, such as age (P = .622), functional status (P = 1.0), disease stage (P = .634), complete response to treatment (P = .572), and survival (P = .492) or with any laboratory parameters including known prognostic factors in SCLC, such as serum sodium or LDH concentration (P values of .731 and .246, respectively). Conclusions and Implications: The presence of anti-p53 antibodies in the serum of patients with newly diagnosed SCLC was not associated with any clinical characteristics or prognostic markers, suggesting that, in this context, the measurement of anti-p53 antibodies is not a useful prognostic marker.