p14ARF protein (FL-132) immunoreactivity in intracranial ependymomas and its prognostic significance: an analysis of 103 cases

Although clinical and histological criteria for ependymoma prognosis are re cognized, studies have reported contradictory results. Prognostic significa nce based on immunohistochemistry of ependymomas has been described in a fe w studies and a strong prognostic value of p53 aberrant expression has been established. Recently, p53 regulation has found to be dependent on the fun ction of the p14ARF gene product, which has been shown to be critically inv olved in human carcinogenesis. In this study we have examined patients with intracranial ependymomas (n=103) for immunoexpression of the novel antibod y FL-132 to human p14ARF protein. We found that: (1) the polyclonal FL-132 antibody seems to be suitable for studying p14ARF protein status in routine ly processed and paraffin-embedded specimens; (2) decreasing p14ARF protein expression is associated with patterns of ependymoma biological aggressive ness, i.e., increasing tumor grade, elevated growth fraction and p53 protei n accumulation; however, there was no any association between p14 and MDM2 immunoexpression in ependymomas; (3) although the biological events underly ing p14ARF inactivation in ependymal neoplasms are still unclear, FL-132 im munohistochemistry appears to be useful for assessing an individual prognos is in these tumors; when the p14 score was considered as "high" versus "low " (cut-off p14 labeling index at 10%), it represented an independent progno stic factor in both univariate and multivariate analyses (hazard ratio -3.5 6; P=0.0003); and (4) most beneficial information for evaluation of maligna nt ependymoma outcome should be elicited from simultaneous immunohistochemi cal investigation of p14 ARF and p53 in tumor specimen.