Expression of heme oxygenase-1 in human glioma

NORBERTO A GANDINI; DEBORA SALOMON; MARIA E FERMENTO; JEAN C ZENKLUSEN; ANA ROBLES; ALEJANDRO CURINO ; MARIA MARTA FACCHINETTI

Miami

Congreso; 6th International Congress on Heme Oxygenases,; 2009

HEME OXYGENASES SOCIETY

The vast majority of experiments performed in different tumor cells indicate that HO-1 is a potent cytoprotective and antiapoptotic enzyme which improves survival of cancer cells subjected to different kinds of therapy. In glioma tumors HO-1 has been shown to be upregulated as compared with normal brain, although the significance of this upregulation is not clear. Therefore, the aim of our study was to perform a wide screening of heme oxygenase-1 (HO1) expression in gliomas by using tissue microarrays (TMA) containing astrocytomas (18), oligodendrogliomas (29), mixed tumors (12), glioblastoma multiforme (GBM, 57) and normal brain (18) and to correlate protein expression with patient clinic pathological data.. HO-1 showed cytoplasmic localization, although a few cells also presented nuclear staining. Nuclear HO-1 was confirmed in T98 and U87 cells. HO-1 was positive in 51% of GBM, 62% astrocytomas, 61% oligodendrogliomas, 42% of mixed and 22% of normal brain tissue. We found differences in HO-1 positivity rates between normal brain and oligodendrogliomas (p=0.012) and astrocytomas (p=0.027). Comparison by the Kaplan-Meier method revealed a significant decrease in overall survival of astrocytoma patients with HO-1 positivity (p=0.03, log rank test). We also performed RT-PCR for mRNA quantification, although no significant differences were observed between normal (n=5) and malignant samples (n=5). In conclusion, our results corroborate higher frequency of HO-1 protein expression in gliomas than in normal brain and show a correlation of HO-1 expression with patient survival.