p73 expression in medulloblastoma: TAp73/DeltaNp73 transcript detection and possible association of p73alpha/DeltaNp73 immunoreactivity with survival
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Child MeSH
- DNA-Binding Proteins genetics immunology metabolism MeSH
- Adult MeSH
- Immunohistochemistry MeSH
- Nuclear Proteins genetics immunology metabolism MeSH
- Humans MeSH
- Medulloblastoma genetics metabolism physiopathology MeSH
- RNA, Messenger analysis metabolism MeSH
- Survival Rate MeSH
- Adolescent MeSH
- Brain metabolism pathology physiopathology MeSH
- Cell Transformation, Neoplastic genetics metabolism MeSH
- Biomarkers, Tumor analysis genetics metabolism MeSH
- Tumor Suppressor Proteins genetics immunology metabolism MeSH
- Brain Neoplasms genetics metabolism physiopathology MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Protein Isoforms genetics isolation & purification metabolism MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Retrospective Studies MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA-Binding Proteins MeSH
- Nuclear Proteins MeSH
- RNA, Messenger MeSH
- Biomarkers, Tumor MeSH
- Tumor Suppressor Proteins MeSH
- Protein Isoforms MeSH
The human p73 protein is essential for normal morphogenesis and maintenance of neural tissue. Recently, several TP73 transcripts have been revealed in medulloblastoma (MB), the most common malignant brain tumor in children. Here, we performed immunohistochemical analysis on 29 MB specimens using anti-p73alpha and anti-DeltaNp73 antibodies. Real-time PCR quantification was performed to assess TAp73 and DeltaNp73 transcripts in a subset of 13 MB samples. Normal cerebellar tissues and RNA were used for comparison. Pilot clinical-pathological correlations were also provided. We report significant differences for TAp73 and DeltaNp73 mRNA expression between tumor tissues and reference (P = 0.013, P = 0.028). Immunohistochemically, 52 and 29% MB samples were positive for p73alpha and DeltaNp73, respectively. p73alpha expression was found to be in both the nucleus and cytoplasm, whereas DeltaNp73 was localized predominantly in the cytoplasm. In normal cerebellum, positive staining for p73alpha and DeltaNp73 was observed in the Purkinje cells of newborns, not adult samples, which supports the developmental role of TP73 during organogenesis of the human cerebellum. Survival analysis has shown negative relationship of DeltaNp73-immunoreactivity with overall survival (OS) and event free survival (EFS) (P = 0.026 and P = 0.127, respectively). For p73alpha-positive cases, the negative trend in OS (P = 0.149) and EFS (P = 0.216) was also apparent. Our results indicate the involvement of p73 protein in MB tumorigenesis and define TP73 as a potential prognostic and therapeutic target for medulloblastoma.
Acta Neuropathol. 2008 Nov;116(5):579-80 PubMed
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