Expression of cell cycle regulator p27Kip1 is correlated with survival of patients with astrocytoma.

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 for astrocytomas. Tissue samples from 130 astrocytomas (WHO grade 1, 5 cases; grade 2, 23 cases; grade 3, 64 cases; grade 4, 38 cases), including 92 primary and 38 recurrent tumors, were examined immunohistochemically for Ki-67 and p27Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The p27Kip1 labeling index (LI) ranged from 2.3 to 98.4%, with a mean value of 47.5% (+/-23.4%). The p27Kip1 LI decreased with increasing tumor grade but did not correlate with other parameters. There was no correlation between Ki-67 LI and p27Kip1 LI. For patients with primary astrocytomas, the 50% survival times of those with low p27Kip1 LI (<50%) and those with high p27Kip1 LI (> or =50%) were 17.1 and 69.6 months, respectively. For patients with high-grade tumors, the 50% survival times were 13.1 months for those with low p27Kip1 LI and 33.7 months for those with high LI. On multivariate analysis, p27Kip1 was one of the most significant prognostic factors, indicating that low p27Kip1 LI was associated with poor prognosis (primary, risk ratio = 2.5, P = 0.0023; high-grade, risk ratio = 2.2; P = 0.0139). The expression of p27Kip1 was inversely related to tumor grade and positively related to favorable outcome of patients with astrocytoma, suggesting that p27Kip1 may be a candidate for prognostic factor for this tumor.