Expression of heme oxygenase-1 in human gliomas

Abstract

The vast majority of experiments performed in different tumor cells indicate that HO-1 is a potent cytoprotective and antiapoptotic enzyme wich improves survival of cancer cells subjected to different kinds of therapy. In glioma tumours 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 glioma 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 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 sgnificant decreasein 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 (n=5). In conclusion, our results corroborate higher frecuency of HO-1 protein expression in gliomas than in normal brain and show a correlation of HO-1 expression with patient survival.