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Distribution of p53 protein expression in gliosarcomas: an immunohistochemical study
S Albrecht1, J H Connelly, J M Bruner
1Department of Pathology, Baylor College of Medicine, Houston, TX.
Abstract:
The wild-type p53 gene product is a nuclear phosphoprotein that suppresses cell and tumor growth. Mutations of the p53 gene are by now the most frequently recognized genetic alterations in human malignancies and occur in many types of carcinomas as well as in astrocytomas and sarcomas. Wild-type p53 protein has a short half-life, is present in very low quantities in normal cells and cannot be detected immunohistochemically. Mutant p53 proteins have longer half-lives and are usually present in immunohistologically detectable amounts. It is generally agreed that the presence of p53 immunostaining indicates the presence of an abnormal p53 protein and is strongly suggestive of a mutation in the p53 gene. In this study, we stained paraffin sections from eight samples of gliosarcomas from seven patients with an antibody to p53. All tumors contained p53-immunoreactive nuclei in both the glial and the sarcomatous component. In five tumors, a majority of nuclei was positive in the sarcomatous component while only a minority of nuclei was positive in the glial areas. In one tumor, the reverse was seen. In another tumor, approximately half the nuclei were positive in both components and in one tumor, only a minority of nuclei were positive in either component (this lesion was the recurrence of a tumor in which the majority of the sarcoma's nuclei had been positive). These data indicate that p53 mutations may play a role in the pathogenesis of gliosarcomas and suggest an origin of both the glial and sarcomatous components from a common progenitor.
Insights
p53 gene mutations are common in human cancers. This study found p53 protein in gliosarcomas, suggesting mutations play a role in tumor development and origin.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 gene product is a tumor suppressor. Mutations in the p53 gene are frequent in human malignancies.
- Wild-type p53 protein is unstable and undetectable in normal cells, while mutant p53 proteins are stable and detectable via immunohistochemistry.
- p53 immunostaining is indicative of p53 gene mutation.
Purpose of the Study:
- To investigate the role of p53 mutations in the pathogenesis of gliosarcomas.
- To determine if p53 protein is expressed in both glial and sarcomatous components of gliosarcomas.
Main Methods:
- Paraffin-embedded tissue sections from eight gliosarcoma samples were stained using an antibody to p53.
- Immunohistochemical analysis was performed to detect p53-immunoreactive nuclei in both tumor components.
Main Results:
- All gliosarcomas examined showed p53-immunoreactive nuclei in both glial and sarcomatous components.
- The proportion of positive nuclei varied between the components and across tumors.
- One recurrent tumor showed a decrease in p53 positivity in the sarcomatous component.
Conclusions:
- p53 mutations likely contribute to the development of gliosarcomas.
- The findings suggest that both glial and sarcomatous elements in gliosarcomas may originate from a common progenitor cell with p53 mutations.