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Absence of p53 autoantibodies in sera from glioma patients
N G Rainov1, K U Dobberstein, M Fittkau
1Department of Neurosurgery, Institute of Pathological Biochemistry, Faculty of Medicine, Martin-Luther-University, Magdeburger Strasse 16, D-06097 Halle (Saale), Halle-Wittenberg, Germany.
Abstract:
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.
Insights
p53 autoantibodies (p53-aAb) are common in many cancers but absent in malignant glioma patients. This suggests brain tumors may evade immune detection, potentially due to impaired immune cells within the tumor microenvironment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Alterations in the p53 tumor suppressor gene are frequent in human cancers, leading to p53 protein overexpression.
- p53 autoantibodies (p53-aAb) are observed in various cancers and can indicate a poor prognosis.
- The presence of p53-aAb in malignant glioma has not been previously investigated.
Purpose of the Study:
- To investigate the presence of p53 autoantibodies (p53-aAb) in patients with malignant glioma.
- To correlate p53 alterations in tumor tissue with p53-aAb serum levels.
Main Methods:
- Sera from 70 glioma patients (WHO G III-IV) and 30 controls were analyzed for p53-aAb using a photometric sandwich-ELISA.
- Tumor tissues were analyzed for p53 gene mutations (exons 5-8) via PCR-SSCP and sequencing.
- Immunohistochemistry was used to detect p53 protein accumulation in tumor cells.
Main Results:
- p53 protein accumulation was detected in 60% of glioma cases.
- p53 gene mutations were found in 39% of glioma cases.
- No p53 autoantibodies (p53-aAb) were detected in any of the malignant glioma patients, contrasting with findings in lung cancer patients.
Conclusions:
- Malignant gliomas are unusual in the lack of serum p53 autoantibodies (p53-aAb), despite common p53 alterations.
- The absence of p53-aAb may be linked to the immunosuppressive environment of brain tumors.
- Further research is needed to understand the mechanisms behind this absent autoimmune response.