Expression of the Ets-1 proto-oncogene correlates with malignant potentialin human astrocytic tumors

The protein encoded by the Ets-l proto-oncogene is a transcription factor t hat regulates expression of matrix proteases. It has been associated with t umor invasion and angiogenesis. Glioma progression is characterized by incr eased invasiveness and neovascularization, so we hypothesized that expressi on of Ets-l proto-oncogene might play a role in the progression of these tu mors. Therefore, we examined the expression of Ets-l protein by immunohisto chemical means and in situ hybridization in tissues obtained from 81 primar y and 20 recurrent astrocytic tumors. Twenty-eight (65%) of 43 glioblastoma s (Grade nr astrocytomas) stained for Ets-l. The percentage of positive cel ls in glioblastomas varied from 10 to 90%. Of the 16 anaplastic astrocytoma s (Grade III), 4 (25%) were moderately positive (<50% of cells) for Ets-l. None of 22 cases of low-grade astrocytomas (Grade II) expressed endogenous Ets-l. The staining score was significantly associated with tumor grade (P <.0001). Normal brain tissues did not express Ets-l protein, whereas recurr ent astrocytoma cases expressed significantly more positivity for Ets-l tha n did primary tumors (P =.03). The Ets-l protein was observed mainly in the nucleus and corresponded to the cytoplasmic Ets-l mRNA localization by in situ hybridization. Western and Northern blot analyses confirmed overexpres sion of Ets-l protein and mRNA in high-grade tumors. We conclude that Ets-l protein expression correlates with the malignant potential of tumors of as troglial origin.