Hammel P, Soussi T
Fédération Médicochirurgicale d'Hépato-Gastroentérologie, Hôpital Beaujon, Clichy, France.
Rev Med Interne. 2000 Feb;21(2):167-73. doi: 10.1016/s0248-8663(00)88246-6.
Alterations of the tumor suppressor gene p53 and its protein synthesis is the most commonly observed genetic feature in human cancers. Direct diagnosis of the gene mutation using sequencing is the gold standard method. However, it requires advanced technology and is only performed in specialized research units.
Demonstration of intratumoral p53 protein accumulation using immunohistochemistry is a routine diagnostic technique. Serum detection of p53 antibodies using ELISA has been recently developed. It is an easily feasible and reproducible method for the diagnosis of p53 alterations due to self-immunization in some patients in response to intratumoral p53 protein overexpression. This phenomenon is inconstant (about one-third of the patients with a p53 gene mutation produce antibodies) and its mechanism is unclear. p53 Antibodies are found in 25% of the patients with colorectal cancer, independently of traditional tumor markers (carcinoembryonic antigen and carbohydrate antigen 19.9). The presence of these antibodies is not linked to the tumor stage. Since their ratios vary during the treatment, they might constitute a new tumor marker.
Early appearance of p53 serum antibodies during tumor development should make them useful for the detection of malignant transformation in patients with preneoplastic disease such as ulcerous colititis. Whether the presence of p53 antibodies in colorectal cancer patients has a prognostic significance requires further assessment.
肿瘤抑制基因p53及其蛋白质合成的改变是人类癌症中最常见的基因特征。使用测序直接诊断基因突变是金标准方法。然而,这需要先进技术,且仅在专业研究单位进行。
使用免疫组织化学证明肿瘤内p53蛋白积累是一种常规诊断技术。最近开发了使用酶联免疫吸附测定法(ELISA)检测血清中的p53抗体。对于诊断某些患者因肿瘤内p53蛋白过表达引起的自身免疫反应导致的p53改变,这是一种易于实施且可重复的方法。这种现象并不恒定(约三分之一的p53基因突变患者产生抗体),其机制尚不清楚。在25%的结直肠癌患者中发现了p53抗体,与传统肿瘤标志物(癌胚抗原和糖类抗原19.9)无关。这些抗体的存在与肿瘤分期无关。由于它们在治疗期间的比例会发生变化,它们可能构成一种新的肿瘤标志物。
肿瘤发展过程中p53血清抗体尽早出现应使其有助于检测患有癌前疾病(如溃疡性结肠炎)患者的恶性转化。结直肠癌患者中p53抗体的存在是否具有预后意义需要进一步评估。