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.


METHODS
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.
Korshunov
Andrey
A
Department of Neuropathology, Burdenko Neurosurgical Institute, Moscow, Russia. akorshunov@nsi.ru
Golanov
Andrey
A
D000328:Adult; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000648:ultrastructure; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000648:ultrastructure; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000648:ultrastructure; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C493971:CDKN2C protein, human; D018797:Cell Cycle Proteins; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins