P53 EXPRESSION IN NEUROFIBROMA AND MALIGNANT PERIPHERAL-NERVE SHEATH TUMOR - AN IMMUNOHISTOCHEMICAL STUDY OF SPORADIC AND NF1-ASSOCIATED TUMORS

Malignant peripheral nerve sheath tumors (MPNST) are highly malignant sarcomas arising either de novo or in transition from neurofibroma. Al though relatively little is known of the molecular genetic alterations that underlie their formation, recent DNA sequencing studies have dem onstrated the presence of p53 mutations in some MPNST. This tumor-supp ressor gene has been implicated in the progression of a variety of hum an malignancies, including sarcomas. Employing the anti-p53 monoclonal antibody Do-7, this retrospective immunohistochemical study of p53 ge ne overexpression in MPNST found reactivity to be present in 68% and t o be significant in degree in 57%. In contrast, although some degree o f p53 overexpression was present in 48% of neurofibromas, none stained strongly and only 1 of the 27 (4%), a cellular example, shelved signi ficant staining. No difference in the frequency or degree of p53 stain ing was noted between MPNSTs from patients with or without neurofibrom atosis I. The observed overexpression of the gene product, possibly th e reflection of a p53 gene mutation, suggests a role for p53 in the pr ogression of neurofibroma to MPNST. Although the prognostic of p53 ove rexpression in MPNST remains to be confirmed, in tile present series i mmunopositive tumors were associated with a shorter median patient sur vival (18 months) than were tumors showing no reactivity (82 months) ( P = .02).