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


METHODS
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.
Korshunov
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Department of Neuropathology, Neurosurgical NN Burdenko Institute, Moscow, Russia. akorshunov@nsi.ru
Golanov
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D000328:Adult; D000951:Antigens, Neoplasm; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009837:Oligodendroglioma / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
D000951:Antigens, Neoplasm; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D004250:DNA Topoisomerases, Type II