The prognostic significance of DNA topoisomerase II-alpha (Ki-S1), p21/Cip-1, and p27/Kip-1 protein immunoexpression in oligodendrogliomas

Arch Pathol Lab Med. 2001 Jul;125(7):892-8. doi: 10.5858/2001-125-0892-TPSODT.

Abstract

Objective: To evaluate a possible association between clinical outcome of patients with oligodendroglioma and expression of 2 cyclin-dependent kinase inhibitors, p21/Cip-1 (p21) and p27/Kip-1 (p27), and of DNA topoisomerase II-alpha (Ki-S1), which has been recently used as a marker of cellular proliferation.

Design: Ninety-one specially selected patients with cerebral oligodendrogliomas treated with surgery and radiotherapy were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p21, p27, and Ki-S1. A computerized color image analyzer was used to count immunostained nuclei.

Results: The mean Ki-S1 labeling index (LI) was found to be significantly prominent for World Health Organization (WHO) high-grade tumors (9.5% vs. 3.2% for WHO low-grade tumors). In contrast, the mean p27 LI was significantly higher for low-grade tumors (43.3% vs 25.7% for high-grade tumors). The number of p21-positive cases and the mean p21 LI were found to be relatively equal for low- and high-grade tumors. For low-grade oligodendrogliomas, the progression-free and overall survival times were found to be significantly shorter for tumors with p27 LIs less than 20%. For high-grade oligodendrogliomas, survival times were significantly reduced for tumors with Ki-S1 LIs greater than 10%. Regression-tree analysis identified 4 groups of oligodendrogliomas with distinctly different outcomes: (1) 32 patients with low-grade tumors and p27 LIs greater than 20%; (2) 14 patients with low-grade tumors and p27 LIs less than 20%; (3) 25 patients with high-grade tumors and Ki-S1 LIs less than 10%; and (4) 20 patients with high-grade tumors and Ki-S1 LIs greater than 10%.

Conclusions: Immunoreactivity for Ki-S1 and p27 was found to be useful for further subdividing oligodendroglioma prognoses among low-grade and high-grade tumors. It seems unlikely that p21 immunohistochemistry will be of value for determining clinical outcomes for patients with oligodendrogliomas.

MeSH terms

  • Adult
  • Antigens, Neoplasm
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • DNA Topoisomerases, Type II* / metabolism*
  • DNA-Binding Proteins
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Oligodendroglioma / metabolism*
  • Oligodendroglioma / pathology
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis

Substances

  • Antigens, Neoplasm
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Isoenzymes
  • DNA Topoisomerases, Type II