p73 expression in medulloblastoma: TAp73/ΔNp73 transcript detection and possible association of p73α/ΔNp73 immunoreactivity with survival

• Published in: Acta neuropathologica 2007-12, Vol.114 (6), p.641-650
• Main Authors: Zitterbart, Karel, Zavrelova, Iva, Kadlecova, Jitka, Spesna, Renata, Kratochvilova, Adela, Pavelka, Zdenek, Sterba, Jaroslav
• Format: Article
• Language: English
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-007-0298-2

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-p73 alpha and anti- Delta Np73 antibodies. Real-time PCR quantification was performed to assess TAp73 and Delta Np73 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 Delta Np73 mRNA expression between tumor tissues and reference (P = 0.013, P = 0.028). Immunohistochemically, 52 and 29% MB samples were positive for p73 alpha and Delta Np73, respectively. p73 alpha expression was found to be in both the nucleus and cytoplasm, whereas Delta Np73 was localized predominantly in the cytoplasm. In normal cerebellum, positive staining for p73 alpha and Delta Np73 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 Delta Np73-immunoreactivity with overall survival (OS) and event free survival (EFS) (P = 0.026 and P = 0.127, respectively). For p73 alpha -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.