FRAT1 expression and its correlation with pathologic grade, proliferation, and apoptosis in human astrocytomas

Abstract

FRAT1 was originally characterized as a protein frequently rearranged in advanced T-cell lymphoma, which inhibits GSK-3-mediated phosphorylation of β-catenin and positively regulates the Wnt signaling pathway. FRAT1 has recently been identified as a proto-oncogene involved in tumorigenesis, as elevated expression of FRAT1 was detected in several types of human cancers. However, the relationship between FRAT1 and human astrocytomas is unclear. In this study, we detected the expression of FRAT1 in 76 patients with human astrocytoma by immunohistochemistry. The proliferative index (PI) of tumor cells was evaluated by Ki-67 staining, and the apoptotic index (AI) was determined by fluorometric TdT-mediated dUTP nick end labeling (TUNEL) assay. The results showed that the FRAT1 immunoreactivity score (IRS), PI, and AI of astrocytoma were 4.11 ± 3.86, 31.92 ± 20.00%, and 2.66 ± 1.66%, respectively, and all of them increased markedly with the increase of pathologic grade of astrocytomas (P < 0.001 for all). The PI in the FRAT1-positive group was significantly higher than that in the FRAT1-negative group (P < 0.001). In addition, the PI was positively correlated with FRAT1 IRS (P < 0.001). Although there was no significant difference between the AI in the FRAT1-positive group and that in the FRAT1-negative group (P = 0.123), the AI was inversely correlated with FRAT1 IRS (P = 0.022). In conclusion, FRAT1 may be an important factor in the tumorigenesis and progression of astrocytoma, which could be used as a potential biomarker for pathological diagnosis of malignancy and a target for biological therapy.