Low expression of p27 indicates a poor prognosis in patients with high-grade astrocytomas

Abstract

Background: Two families of tumor suppressor genes, Cip/Kip (p21, p27, and 57) and INK4 (p15, p16, p18, and p19), regulate cell proliferation and neoplastic transformation. p27 exerts its suppressor effect through cyclin E-dependent kinase (CDK2) by inhibiting the phosphorylation of pRb by CDK2, which, in turn, arrests cells in the G1-phase. p21 has a similar effect in addition to participating in the p53 dependent CDK4-mediated and CDK6-mediated pathway. The authors studied the prognostic significance of p21 and p27 in patients with high-grade astrocytomas who were treated with radiotherapy.

Methods: The expression of p27 and p21 was analyzed immunohistochemically in 52 glioblastomas and 25 anaplastic astrocytomas. All patients underwent surgery for the first time and were treated with adjuvant external radiotherapy.

Results: The p27 labeling index (LI) was < 30% in 36% of tumors, 30-50% in 25% of tumors, and > 50% in 39% of tumors. A significant difference in cumulative survival was observed between these groups (P = 0.0072; log-rank test). The p21 LI was < 30% in 48% of tumors, 30-50% in 39% of tumors, and > 50% in 13% of tumors; these groups did not differ significantly in survival. In multivariate Cox analysis, p27 LI was an independent prognostic factor (P = 0.0008). The grade of malignancy and proliferation activity also were independent prognostic factors.

Conclusions: Although p27 and p21 are parallel cell-cycle regulators, only p27 has independent prognostic value in patients with malignant astrocytomas. It appears that decreased levels of p21/p27 are associated with a poor prognosis and short survival.