Immunohistochemical analysis of p18INK4C and p14ARF protein expression in 117 oligodendrogliomas: correlation with tumor grade and clinical outcome.

OBJECTIVE: To investigate immunoexpression of 2 cyclin-dependent kinase inhibitors, p18INK4C (p18) and p14ARF (p14), in oligodendrogliomas and to evaluate the possible association with tumor grade and clinical outcome.
DESIGN: One hundred seventeen specially selected cases of cerebral oligodendrogliomas were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p18INK4C (118.2) and p14ARF (FL-132) proteins. A computerized color image analyzer was used to count immunostained nuclei.
RESULTS: p18 nuclear immunoexpression was found in 57 (49%) of the oligodendrogliomas we studied. p18 immunoreactivity exhibited a clear tendency to elevate with increasing tumor grade, and the mean p18 labeling index was 9.7% for low-grade (World Health Organization [WHO] grade II) and 19.2% for high-grade (WHO III) tumors. p14-immunopositive nuclei were found in 87 (74%) tumors, and p14 immunoreactivity showed no correlation with oligodendroglioma histological malignancy. Survival times were significantly reduced for p18-positive tumors, and risk of death was independently associated with p18 expression (hazard ratio = 2.48; P =.01). There was no difference in survival times in patients with or without p14 immunoreactivity.
CONCLUSIONS: p18 protein expression is closely associated with malignant oligodendrogliomas and worse clinical outcome. It seems unlikely that p14 immunohistochemistry will be of value in assessing individual prognosis for these tumors.