ATPase-INHIBITORY FACTOR 1 IS A PROGNOSTIC FACTOR IN LOW GRADE ASTROCYTOMAS

The purpose of the study was to investigate the expression levels and the prognostic value of ATPase-Inhibitory Factor 1 (IF1), the regulatory protein of mitochondrial ATPsynthase, in human WHO grade II gliomas, which still need to be categorized as high or low risk. Surgical specimens of astrocytomas (LGA), from patients well characterized by state-of-the-art clinical, histological and molecular parameters, were analysed for IF1. Evaluation of the tumor border zone from 19 specimens showed significantly greater IF1 values in the tumoral zone. Immunohistochemistry analyses of 71 specimens by Tissue-MicroArrays proved a positive correlation of IF1 with NFkB p65-subunit expression. Kaplan–Meier estimation of patients overall survival indicated that IF1 may serve as a prognostic marker. Intriguingly, IF1 expression significantly increased in lesions with first signs of anaplastic transformation (LGA*) as showed, in accordance, by immunofluorescence (12 specimens), immunohistochemistry (49) and immunoblot (9) analyses. Finally, immunoblot analyses provided a picture of mitochondrial and glycolytic markers, delineating metabolic phenotype changes in LGA* and suggesting no improvement of glycolysis. In conclusion, IF1 might be considered as a new sensitive predictor of poor prognosis for LGA/LGA*, in analogy with carcinomas and high grade gliomas [1-5], and a non-canonical IF1 role in LGA progression might emerge.