© 2002 by Society
© 2002 by the Society forNeuro-Oncology
MDM2 overexpression is associated with short survival in adults withmedulloblastoma
Department of Neuroscience, University of Turin, 10126 Turin,Italy
2 Address correspondence and reprint requests to Maria Teresa Giordana,Department of Neuroscience, University of Turin, Via Cherasco 15, 10126Torino, Italy;mariateresa.giordana{at}unito.it.
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Abstract |
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In adult medulloblastoma, postoperative radiotherapy is significantlyeffective in prolonging time to recurrence and survival time; however, theresponse of individual cases to radiotherapy, that is the total survival, isdifferent. Apoptosis is an important cellular response to radiation. It can behypothesized that the individual radiosensitivity of medulloblastomas dependson the individual capability to undergo apoptosis. p53 protein is involved inthe apoptotic response to ionizing radiation; loss of function of p53 can bethe consequence not only of TP53 mutations, but also of amplificationand/or overexpression of the MDM2 gene. We have analyzed cerebellarmedulloblastomas from 51 adults (>16 years of age) for MDM2 geneamplification (by differential polymerase chain reaction assay), TP53gene mutation (by polymerase chain reaction single-strand conformationpolymorphism analysis of exons 5-8), and immunohistochemical expression of p53(clone DO1) and MDM2 (clone IF2). The results have been evaluated inrelation to age, tumor location, classic or desmoplastic type, MIB-1 labelingindex, and total survival. No tumor had MDM2 amplification. Tentumors had MDM2-positive tumor cells. One case had a mutatedTP53 gene; 16/51 cases had intense p53 immunostaining. Only 2MDM2 protein-positive tumors were also p53-positive. Both subgroupsof MDM2- and p53-positive tumors had a significantly shorterpostoperative survival. In conclusion, the overexpression of MDM2protein and the accumulation of wild-type p53 are unrelated in adultmedulloblastoma; they may result in a reduced apoptotic response afterradiotherapy and contribute to a shortened survival. Also, MDM2amplification and TP53 gene mutation are rare events inmedulloblastomas of adults.
Received November 19, 2001; Accepted December 20, 2001
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