Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus.
BACKGROUND
p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined.


METHODS
p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction.


RESULTS
p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected.


CONCLUSIONS
Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.
Eberhart
Charles G
CG
Department of Pathology, Johns Hopkins University School of Medicine, Ross Bldg 558, 720 Rutland Ave, Baltimore, MD 21205, USA. ceberha@jhmi.edu
Chaudhry
Aneeka
A
Daniel
Richard W
RW
Khaki
Leila
L
Shah
Keerti V
KV
Gravitt
Patti E
PE
D000293:Adolescent; D000328:Adult; D000708:Anaplasia; D002528:Cerebellar Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007577:JC Virus / Q000302:isolation & purification*; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D008875:Middle Aged; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015173:Supratentorial Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D013724:Teratoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53
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