Wnt signaling transcription factors TCF-1 and LEF-1 are upregulated in malignant astrocytic brain tumors

Nives Pećina-Šlaus^1,2, Anja Kafka^1,2, Davor Tomas^3,4, Leon Marković¹, Petar Krešimir Okštajner¹, Viktorija Sukser¹ and Božo Krušlin<sup>3,4

1</sup>Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia, ²Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia, ³Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia and ⁴University Hospital "Sisters of Charity", Zagreb, Croatia

Offprint requests to: Nives Pećina-Šlaus, Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 12, HR-10000 Zagreb, Croatia. e-mail: nina@mef.hr

Summary. Since the discovery of the TCF/LEF family of transcription factors, their functions have been under intensive investigation in the area of cancer biology. The work presented in this paper focused on the changes in TCF-1 and LEF-1 expression levels in a set of astrocytic brain tumors. Protein expression was detected using immunohistochemistry and then evaluated by Ellipse software (ViDiTo, Slovakia). Statistical evaluations were performed with the SPSS statistical package, version 14.0 (SPSS Inc., Chicago, IL, USA). Strong TCF-1 and LEF-1 expression was observed in 51.6% and 71% of glioblastoma samples. Statistical analysis confirmed significant differences in protein expression levels associated to 3 important values, weak expression of TCF-1, weak expression of LEF-1 and strong expression of LEF-1. Analysis of variances performed on the total sample also indicated significant differences in the values of TCF-1 weak (F=2.804; p=0.045), LEF-1 weak (F=4.255; p=0.008) and LEF-1 strong (F=5.498; p=0.002) with regard to malignancy grade. Thus, glioblastomas were characterized by –in relative terms- the lowest values for weak expression of TCF-1 and LEF-1, combined with the highest values of LEF-1 strong expression. The F-ratios for two variables (LEF-1 strong and LEF-1 weak) indicated that differences between astrocytomas (II, III) and glioblastomas were statistically significant (p<0.02). Discriminant function analysis further showed that strong LEF-1 expression alone could discriminate between astrocytomas (II, III) and glioblastomas. Elevated TCF-1 and LEF-1 expression is characteristic of malignant gliomas. LEF-1, in particular, may serve as a potential marker for malignant transformation. Histol Histopathol 29, 1557-1564 (2014)

Key words: Astrocytic brain tumors, Glioblastoma, Transcription factors TCF-1, LEF-1, Wnt signaling

DOI: 10.14670/HH-29.1557