Significantly higher expression of high-mobility group AT hook protein 2 (HMGA2) in the border zone of glioblastoma.

ABSTRACT

BACKGROUND: High-mobility group AT-hook protein 2 (HMGA2) is a gene regulatory protein that is correlated with metastatic potential and poor prognosis. It has been shown that HMGA2 is overexpressed in various tumors such as lung cancer or pancreatic cancer. The invasive character and highly aggressive structure of glioblastoma let us to investigate HMGA2 expression in the border zone of the tumor more closely. We compared HMGA2 expression between glioblastoma and normal brain tissue. In addition, we analyzed and compared HMGA2 expression in the border and center zones of tumors. Correlation tests between HMGA expression and clinical parameters such as MGMT-status and survival were performed. METHODS: Samples from 23 patients with WHO grade 4 glioblastomas were analyzed for HMGA2 expression using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) and correlated with clinical parameters. The areas from the tumor center and border were analyzed separately. Two normal brain tissue specimens were used as the controls. RESULTS: Our results confirm that HMGA2 is higher expressed in glioblastoma compared to healthy brain tissue (qPCR, P=0.013; IHC, P=0.04). Moreover, immunohistochemistry revealed significantly higher HMGA2 expression in the border zone of the tumor than in the tumor center zone (P=0.012). Survival analysis revealed a tendency for shorter survival when HMGA2 was highly expressed in the border zone. CONCLUSIONS: The results reveal an overexpression of HMGA2 in the border zone of glioblastomas; thus, the expression cluster of HMGA2 seems to be heterogenous and thorough borough surgical resection of the vital and aggressive border cells might be important to inhibit the invasive character of the tumor.