Trivers G E, Cawley H L, DeBenedetti V M, Hollstein M, Marion M J, Bennett W P, Hoover M L, Prives C C, Tamburro C C, Harris C C
Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892, USA.
J Natl Cancer Inst. 1995 Sep 20;87(18):1400-7. doi: 10.1093/jnci/87.18.1400.
The p53 tumor suppressor gene (also known as TP53) is often mutated in a wide variety of cancers, including angiosarcoma of the liver (ASL). Anti-p53 antibodies have been detected in the sera of patients with leukemia, childhood lymphoma, or cancers such as those of the breast, lung, colon, esophagus, and liver (hepatocellular carcinoma).
The objective of this study was to determine the prevalence and time of appearance of serum anti-p53 antibodies during the pathogenesis of ASL associated with occupational exposure to vinyl chloride.
Enzyme-linked immunoassay (EIA) was used to detect anti-p53 antibodies in 148 serum samples from 92 individuals occupationally exposed (in France or in Kentucky) to vinyl chloride; 15 of these individuals (six from France and nine from Kentucky) had ASL. A subset of coded EIA-positive and EIA-negative sera was further analyzed for anti-p53 antibodies by immunoblotting and immunoprecipitation. Nucleotide sequence analysis of exons 5-8 of the p53 gene was conducted on ASL DNA from six patients. We tested sera from 31 men who had no occupational exposure to vinyl chloride; they made up the control group. Statistical analyses were done using the Kruskal-Wallis chi-squared approximation and the Wilcoxon two-sample test for normal approximation. All P values result from two-sided tests.
Fourteen serum samples (from nine individuals) were positive in the EIA. Five of the 15 individuals with ASL were positive for anti-p53 antibodies by EIA, immunoblotting, and immunoprecipitation: one individual at 11.3 and 10.8 years before diagnosis, another at 4 months before and shortly after diagnosis, and three when diagnosed or shortly thereafter. Four of the 77 vinyl chloride-exposed workers without diagnosed ASL were positive for anti-p53 antibodies; two of the four had symptoms related to vinyl chloride toxicity. Tumors from three of the six vinyl chloride-exposed workers from which sufficient DNA for analysis was obtained had A:T to T:A missense mutations of the p53 gene. Anti-p53 antibodies were detected in two of these individuals. Among the control group, two of 15 serum samples from 15 lung cancer patients and zero of 15 serum samples from control subjects without cancer had anti-p53 antibodies as substantially lower levels than the nine (10%) of 92 vinyl chloride-exposed workers who were positive for anti-p53 antibodies.
Serum anti-p53 antibodies can predate clinical diagnosis of certain tumors, such as ASL, and may be useful in identifying individuals at high cancer risk, such as workers with occupational exposure to vinyl chloride.
p53肿瘤抑制基因（也称为TP53）在包括肝血管肉瘤（ASL）在内的多种癌症中常发生突变。在白血病、儿童淋巴瘤患者或乳腺癌、肺癌、结肠癌、食管癌及肝癌（肝细胞癌）等癌症患者的血清中已检测到抗p53抗体。
本研究的目的是确定与职业性接触氯乙烯相关的ASL发病过程中血清抗p53抗体的患病率及出现时间。
采用酶联免疫吸附测定（EIA）检测92名职业性接触（在法国或肯塔基州）氯乙烯的个体的148份血清样本中的抗p53抗体；其中15名个体（6名来自法国，9名来自肯塔基州）患有ASL。对编码的EIA阳性和EIA阴性血清的一个子集通过免疫印迹和免疫沉淀进一步分析抗p53抗体。对6例患者的ASL DNA进行p53基因外显子5 - 8的核苷酸序列分析。我们检测了31名无职业性氯乙烯接触史男性的血清；他们组成对照组。使用Kruskal - Wallis卡方近似法和Wilcoxon双样本正态近似检验进行统计分析。所有P值均来自双侧检验。
在EIA中，14份血清样本（来自9名个体）呈阳性。15例ASL患者中有5例通过EIA、免疫印迹和免疫沉淀检测抗p53抗体呈阳性：1例在诊断前11.3年和10.8年呈阳性，另1例在诊断前4个月及诊断后不久呈阳性，3例在诊断时或诊断后不久呈阳性。77名未诊断出ASL的氯乙烯接触工人中有4例抗p53抗体呈阳性；这4例中有2例有与氯乙烯毒性相关的症状。在6名有足够DNA用于分析的氯乙烯接触工人中，有3例的肿瘤存在p53基因的A:T到T:A错义突变。其中有两名个体检测到抗p53抗体。在对照组中，15例肺癌患者的15份血清样本中有2份、15名无癌症的对照受试者的15份血清样本中无一例检测到抗p53抗体，其水平明显低于92名抗p53抗体呈阳性的氯乙烯接触工人中的9例（10%）。
血清抗p53抗体可能在某些肿瘤如ASL的临床诊断之前出现，可能有助于识别癌症高危个体，如职业性接触氯乙烯的工人。
