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Expression of Cell Cycle Regulator p27^Kip1 Is Correlated with Survival of Patients with Astrocytoma¹

Department of Neurological Surgery, Okayama University Medical School, Okayama 700-8558, Japan

p27^Kip1 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 p27^Kip1 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 p27^Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The p27^Kip1 labeling index (LI) ranged from 2.3 to 98.4%, with a mean value of 47.5% (± 23.4%). The p27^Kip1 LI decreased with increasing tumor grade but did not correlate with other parameters. There was no correlation between Ki-67 LI and p27^Kip1 LI. For patients with primary astrocytomas, the 50% survival times of those with low p27^Kip1 LI (<50%) and those with high p27^Kip1 LI (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 p27^Kip1 LI and 33.7 months for those with high LI. On multivariate analysis, p27^Kip1 was one of the most significant prognostic factors, indicating that low p27^Kip1 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 p27^Kip1 was inversely related to tumor grade and positively related to favorable outcome of patients with astrocytoma, suggesting that p27^Kip1 may be a candidate for prognostic factor for this tumor.

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