Expression of p27kip1 and p53 in medulloblastoma: Relationship with cell proliferation and survival

p27kip1 and p21cip1 are cyclin-dependent kinase (cdk) inhibitors which alon g with p53 play critical roles in the control of cell cycle progression. Ac cumulation of p27kip1 in post-mitotic neurons is a major event of neurogene sis. We hypothesized that a dysregulation of the expression of p53 and thes e cdk inhibitors underlies cellular proliferation in medulloblastomas, and tested this hypothesis by investigating p27kip1, p21cip1, Bcl2 and p53 immu noreactivity in 14 medulloblastoma tumors. We noted an inverse relationship between p27kip1 expression and cellular proliferation (MIB1). Focal island s of neuroblastic or glial differentiation expressed high levels of p27kip1 , while the undifferentiated, highly-proliferative population of tumor cell s showed no detectable p27kip1 expression, thus suggesting a role for p27ki p1 in cell cycle control in medulloblastoma. In addition, there was no dete ctable p21cip1 expression in any of the medulloblastomas studied. The low l evel of apoptosis displayed by these tumors was not associated with the exp ression of Bcl-2. A significant relationship was found between detection of p53 protein and poor survival. Since: p21cip1 and p27kip1 are often co-exp ressed with other INK4 family of cdk inhibitors during the induction of cel lular differentiation and are synergistic in their effect, a deregulation o f their coordinate expression may underlie the lack of complete differentia tion in medulloblastoma.