p53 in nonneoplastic CNS lesions: an immunohistochemical and gene sequencing study

Ö Kurtkaya-Yapicier, M.D.a,b, BW Scheithauer, M.D.b, CD James, Ph.D.

a Marmara University, Istanbul, Turkey; b Mayo Clinic, Rochester, MN

AIM: Immunostaining for p53 protein is commonly considered an indicator of neoplasia. Indeed, p53 antisera are marketed as such. Studies of p53 immunoexpression in non-neoplastic processes have yielded conflicting results. METHODS: To assess the assumption that p53 is a neoplastic marker, we examined its immunoexpression in formalin-fixed, paraffin-embedded biopsies of non-neoplastic brain lesions, including gliosis (n=12), demyelinating disease (n=23), progressive multifocal leukoencephalopathy (PML) (n=11), infarction (n=9), and herpes simplex encephalitis (HSV) (n=6). Diffuse astrocytomas (n=50) of varying grade were also assessed. For immunohistochemistry, the ABC method was employed using two commercially available antisera (p53-DO7, DAKO; mdm2, DAKO). Immunoreactivity was scored as follows: 1+ = <25%, 2+ = 25-50%, 3+ = 50-75%, 4+ = >75%. Four samples of each lesion were also subject to DNA isolation and amplification followed by sequencing of exons 5-8 of the p53 gene. RESULTS: p53 immunoreactivity was noted in all in samples, non-neoplastic and neoplastic. In the former, staining was limited to reactive astrocytes, histiocytes where present, and endothelial cells. The scores were as follows: gliosis 2+, demyelinating disease 2+, PML 3+, infarction 2+, HSV 1-2+. All astrocytomas were immunopositive, particularly grades 3 and 4. Reactivity for mdm2, studied only in non-neoplastic lesions, was seen in all cases. More intense than p53 staining, it was limited to reactive astrocytes and histiocytes. No p53 gene mutations were noted in any lesion. CONCLUSION: In summary, a) p53 immunoreactivity is not limited to astrocytomas, but is commonly seen in reactive and infectious lesions, b) mdm2 may be responsible for persistence of p53 protein, and c) no p53 mutations accompany overexpression of this protein in non-neoplastic lesions.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Molecular Pathology.