The role of p53 gene mutations in the formation or progression of human ast
rocytic tumors is controversial. We studied the distribution pattern of p53
immunoreactivity and analyzed p53 gene mutations to define the significanc
e of p53 gene mutations in astrocytoma tumorigenesis or malignant progressi
on. Twenty three astrocytic tumors were evaluated with immunohistochemistry
, single-strand conformation polymorphism (SSCP) analysis, and sequence ana
lysis. We also searched MEDLINE to collect data on p53 gene mutation freque
ncies in astrocytic tumors in order to evaluate the association of p53 muta
tions and tumor grade. Strong immunoreactivity with a diffuse clustering pa
ttern was found in three of five glioblastomas and seven of 12 anaplastic a
strocytomas. Three of four low-grade astrocytomas were immunonegative. The
p53 immunopositive cells in the only positively staining low-grade astrocyt
oma in our study appeared sparsely scattered. The results of immunostaining
suggested that clonal expansion was associated with astrocytoma progressio
n. Mutations of the p53 gene were detected in four of the 23 astrocytomas t
one glioblastoma and three anaplastic astrocytomas). In the genetic data an
alysis, 76 of 367 astrocytomas had p53 gene mutations. A significantly grea
ter p53 gene mutation frequency was found in anaplastic astrocytomas or gli
oblastomas than in die low-grade astrocytomas. The results of these immunoh
istochemical and genetic studies support the view that p53 gene mutation is
associated with the malignant progression from low-grade to high-grade ast
rocytomas rather than with tumor initiation or promotion.