Expression of chemoresistance markers in glioblastoma (GBM) and in peritumoral tissue

The mechanisms responsible for resistance to damage in normal cells might determine chemoresistance in both tumor cells and cancer stem cells (CSC). Increasing body of evidence indicates that both tumor area (TT) and tissue surrounding the tumor border (pTT) of GBM contain tumor cells and CSC. Therefore, the need to have a deeper insight in pTT through identification of the characteristics that confer tumor resistance to conventional therapies. In this study, the expression of O6-methylguanine-DNA methyltransferase (MGMT), a suicid-al DNA repair protein, Breast Cancer Resistance Protein (BCRP1), a drug efflux transporter, and A2B5 (c-series gangliosides expressed in CSC) has been determined by immunohisto-chemistry in samples derived from TT and from pTT at <1 cm from the tumor border, in 40 patients with GBM. The percentage of MGMT positive cells was higher (p<0.0001, paired Student's t test) in pTT (median: 53.5, range: 0.6-92.4) with respect to TT (median: 3.3, range: 0.0-70.7). The same trend was observed in BCRP1 expression (p<0.02; pTT, median: 27.6, range: 1.0-95.6; TT, median: 10.1, range: 0.2-72.1). No difference was found between pTT and TT in A2B5 ex-pression (p=0.69, pTT, median: 29.8, range: 0.0-98.4; TT, median: 26.0, range: 0.0-96.8). Pa-tients were then divided into two groups according to presence (A) or absence (B) of tumor cells in pTT. The trend previous observed in MGMT expression was maintained in both groups, while only in group A a statistically significant difference in BCRP1 expression was observed. Our results confirm that the tissue surrounding GBM represents a frontline of tumor invasion, particularly for the presence (higher expression with respect to the tumor) of some molecules involved in GBM resistance to the conventional treatments. Experiments about the expression of above mentioned molecules in CSC derived from both pTT and TT are in progress. Supported by FIRB, Accordi di Programma 2010