Inverse correlation of TRF1 expression and cell proliferation in human primary intracranial tumors.

ABSTRACT

BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling cellular proliferative potential. TRF1 is involved in a negative feedback mechanism that allows telomere shortening by inhibiting the activity of telomerase. Down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. The goal of the present study was to determine whether routine immunohistochemical (IHC) techniques can characterize TRF1 expression in different human brain tumor specimens and whether it correlates with other indices of brain tumor's proliferative potential. METHODS: A cohort of 20 flash-frozen surgical specimens [14 meningiomas and 6 anaplastic astrocytomas (AA)] were evaluated for TRF1 expression. Results of parallel investigations of tumor's proliferative indices as assessed by Ki67 labeling index (LI) determinations were cross-correlated with TRF1 expression results and histotype. RESULTS: We demonstrated variable levels of TRF1 expression in 12 out of 14 (87.5%) meningioma samples. By contrast, we detected no expression of TRF1 in tissue samples from AA (p=0.008). The Ki67 LI was higher in AA than in meningioma samples (15.21+/-9.34 vs 26.6+/-13.89, p=0.044). Statistical analysis revealed a significant inverse correlation between TRF1 expression, histotype, and LI (c2=14.1; p=0.0008). CONCLUSIONS: We demonstrated for the first time that routine IHC techniques are capable to identifying TRF1 expression in intracranial tumors. The results suggest that TRF1 is heterogeneously expressed in meningiomas, and absent in AA. The TRF1 status in intracranial tumors might be of prognostic value and possibly represent a potential application for biologically targeted therapeutic strategies.