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

Mutations in the TP53 tumor suppressor gene have been studied in diffe rent types of brain tumors. Little is known about this genetic event i n human meningioma, a mostly benign tumor. To investigate the frequenc y of TP53 gene mutations in human tumors derived from meningeal tissue s, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiop ericytomas) were screened by immunohistochemistry. Polymerase chain re action/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p 53 staining was not seen in any of the 19 benign meningiomas tested, w hile 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 me ningioma 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 c hanging GCC to ACC and resulting in an alteration of alanine to threon ine 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. (C) 1995 Wiley-Liss, Inc.