title: Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples.
abstract: Mutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.
authors.affiliation: Department of Pathology, University Hospital, Uppsala, Sweden.
authors.forename: J L
authors.initials: JL
authors.lastname: Wang
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Hartman
authors.forename: A
authors.initials: A
authors.lastname: Smits
authors.forename: B
authors.initials: B
authors.lastname: Westermark
authors.forename: C
authors.initials: C
authors.lastname: Muhr
authors.forename: M
authors.initials: M
authors.lastname: Nistér
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010232:Paraffin; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D017931:DNA Primers; D010232:Paraffin