Rainov N G, Dobberstein K U, Fittkau M, Bahn H, Holzhausen H J, Gantchev L, Burkert W
Department of Neurosurgery, Institute of Pathological Biochemistry, Faculty of Medicine, Martin-Luther-University, Magdeburger Strasse 16, D-06097 Halle (Saale), Halle-Wittenberg, Germany.
Clin Cancer Res. 1995 Jul;1(7):775-81.
Alteration of the tumor suppressor gene p53 is the most frequent genetic feature of human cancer and leads to over-expression and loss of function of the p53 protein in affected cells. Patients with many types of cancer, including breast, lung, and colon carcinoma, were shown to develop auto-immune response against the overexpressed protein and to produce autoantibodies directed to immunodominant epitopes common for both wild type and mutants. The presence of p53 autoantibodies (p53-aAb) seems to be, at least in patients with breast and bronchial tumors, related to an unfavorable prognosis. The present study aimed to investigate the presence of p53-aAb in patients with malignant glioma. Sera from 70 consecutive patients with gliomas graded WHO G III and IV were collected and assayed together with sera from 30 controls. A new photometric sandwich-ELISA was used for semiquantitative analysis of p53-aAb titers. p53 gene and its protein product were examined in formalin-fixed and fresh-frozen tumor tissues using immunohistochemistry, PCR-single-strand conformational polymorphism, and sequencing. Sixty percent of the glioma cases showed immunohistochemically positive cells, thus indicating intracellular accumulation of p53. Sequencing of the hot-spot exons 5-8 revealed mutations in 39% of the tumor cases. In contrast to results in other types of malignant tumors, where up to 40% of patients have high serum titers of p53-aAb, no such antibodies were found in patients with malignant cerebral glioma despite the presence of mutated or alterated p53 protein in the primary tumors. None of the non-cancer control patients had detectable titers of p53-aAb, although sera from five of six lung cancer patients had medium to high titers. The presented data suggest that glial tumors are unusual in the absence of serum antibodies to p53. It is hypothesized that impaired function of most immunocompetent cells invading brain tumors could be the cause for the absence of an autoimmune response.
肿瘤抑制基因p53的改变是人类癌症最常见的遗传特征，会导致受影响细胞中p53蛋白的过度表达和功能丧失。包括乳腺癌、肺癌和结肠癌在内的多种癌症患者，被证明会针对过度表达的蛋白产生自身免疫反应，并产生针对野生型和突变体共有的免疫显性表位的自身抗体。p53自身抗体（p53-aAb）的存在似乎至少在乳腺癌和支气管肿瘤患者中与不良预后相关。本研究旨在调查恶性胶质瘤患者中p53-aAb的存在情况。收集了70例连续的世界卫生组织G III级和IV级胶质瘤患者的血清，并与30例对照者的血清一起进行检测。一种新的光度夹心酶联免疫吸附测定法用于p53-aAb滴度的半定量分析。使用免疫组织化学、聚合酶链反应-单链构象多态性和测序技术，在福尔马林固定和新鲜冷冻的肿瘤组织中检测p53基因及其蛋白产物。60%的胶质瘤病例显示免疫组织化学阳性细胞，从而表明p53在细胞内积聚。热点外显子5-8的测序显示39%的肿瘤病例存在突变。与其他类型恶性肿瘤的结果不同，在其他类型恶性肿瘤中高达40%的患者血清中p53-aAb滴度较高，尽管原发性肿瘤中存在突变或改变的p53蛋白，但恶性脑胶质瘤患者中未发现此类抗体。六例肺癌患者中有五例的血清具有中到高滴度，但非癌症对照患者中无一例检测到可检测到的p53-aAb滴度。所呈现的数据表明，胶质肿瘤在缺乏针对p53的血清抗体方面是不寻常的。据推测，侵入脑肿瘤的大多数免疫活性细胞功能受损可能是缺乏自身免疫反应的原因。
