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Acta Neuropathol (2007) 114:641650 DOI 10.1007/s00401-007-0298-2
ORIGINAL PAPER
p73 expression in medulloblastoma: TAp73/[afii9797]Np73 transcript detection and possible association of p73[afii9825]/[afii9797]Np73 immunoreactivity with survival
Karel Zitterbart Iva Zavrelova Jitka Kadlecova Renata Spesna Adela Kratochvilova
Zdenek Pavelka Jaroslav Sterba
Received: 7 August 2007 / Revised: 13 September 2007 / Accepted: 15 September 2007 / Published online: 3 October 2007 Springer-Verlag 2007
Abstract 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[afii9825] and anti-[afii9797]Np73 antibodies. Real-time PCR quantiWcation was performed to assess TAp73 and [afii9797]Np73 transcripts in a subset of 13 MB samples. Normal cerebellar tissues and RNA were used for comparison. Pilot clinicalpathological correlations were also provided. We report signiWcant diVerences for TAp73 and [afii9797]Np73 mRNA expression between tumor tissues and reference (P = 0.013, P = 0.028). Immunohistochemically, 52 and 29% MB samples were positive for p73[afii9825] and [afii9797]Np73, respectively. p73[afii9825] expression was found to be in both the nucleus and cytoplasm, whereas [afii9797]Np73 was localized predominantly in the cytoplasm. In normal cerebellum, positive staining for p73[afii9825] and [afii9797]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 [afii9797]Np73-immunoreactivity with overall
survival (OS) and event free survival (EFS) (P = 0.026 and P = 0.127, respectively). For p73[afii9825]-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 deWne TP73 as a potential prognostic and therapeutic target for medulloblastoma.
Keywords Medulloblastoma Isoforms of p73 protein TP73 Cerebellum Prognosis
Introduction
Medulloblastoma (MB), an embryonal neuroectodermal tumor of the cerebellum, is the most common malignant brain tumor in children. Recent advances in multimodal treatments have improved 5-year survival rates substantially and more than 7080% of children with average risk MB are expected to be cured. However, survival has remained poor for high-risk patients and 5-year cure rates of approximately 3563% have been reported for this group, with signiWcant late eVects for many survivors...