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Malignant astrocytoma remains incurable and rapidly fatal despite multimodal therapy. In particular, accelerated tumor cell heterogeneity often overcomes therapeutic effects of molecular protein targeting. This study aimed at identifying a gene with therapeutic potential that was consistently downregulated with astrocytoma progression. Analysis of the "Rembrandt" gene expression data revealed Wnt inhibitory factor 1 (WIF1) gene as the most promising candidate with tumor suppressor function. Consequently, 288 randomly selected tissue regions of astrocytoma specimens were investigated immunohistochemically with the aid of image analysis. This in situ approach identified tumor areas with numerous single cells strongly expressing Wif-1. In diffuse and anaplastic astrocytoma, the proliferation index was independent of the generally weak Wif-1 expression in tumor cells but was significantly correlated with the density of Wif-1-expressing single cells, subsequently characterized as native and non-neoplastic oligodendrocytes. Because these cells may contribute to inhibition of tumor cell proliferation by paracrine signaling, the endogenous protein Wif-1 may represent a promising therapeutic agent with expected minimal side effects. Moreover, we suggest that immunohistochemistry for Wif might be useful for discriminating between astrocytic tumors and reactive changes.

Native Oligodendrocytes in Astrocytomas Might Inhibit Tumor Proliferation by WIF1 Expression