Immunohistochemical expression of Ets-1 transcription factor and the urokinase-type plasminogen activator is correlated with the malignant and invasive potential in meningiomas.
BACKGROUND
The Ets-1 transcription factor has been proposed to play an important role in the invasive process of tumor cells through the induction of urokinase-type plasminogen activator (u-PA).


METHODS
Because meningiomas are potentially invasive tumors, irrespective of their malignancy grades, the authors immunohistochemically investigated Ets-1 and u-PA expression in tissues obtained from 50 benign (16 meningotheliomatous, 14 fibrous, 13 transitional, 6 angiomatous, and 1 microcystic), 4 atypical, and 6 anaplastic meningiomas and correlated their results with the malignancy and invasive potential.


RESULTS
Ets-1 protein was expressed in 19 of the benign meningiomas (38%)whereas 31 (62%) were u-PA positive. The percentage of positive cells frequently was < 50%. In contrast, Ets-1 and u-PA expression was observed in all 4 atypical (100%) and all 6 anaplastic (100%) cases, respectively. The proportion of cells positive for Ets-1 and u-PA frequently were > or = 50%. A significant difference was observed between Ets-1 and u-PA expression in benign and high grade meningiomas (P < 0.0001). Moreover, Ets-1 expression was found to correlate significantly with u-PA positivity in meningiomas (P < 0.0001). Twenty-one of 60 meningioma cases (35%) showed infiltration either to the brain, dura mater, or bone. Eighteen of these 21 cases (85.7%) were positive for Ets-1 and u-PA. Ets-1 and u-PA positivity was found to correlate well with the invasive phenotype in meningiomas (P < 0.001).


CONCLUSIONS
The findings of the current study support the possibility that the Ets-1 transcription factor, through u-PA induction, may be involved in the invasive process in meningiomas.
Kitange
G
G
Department of Neurosurgery, Nagasaki University School of Medicine, Japan. kitange.gaspar@mayo.edu
Tsunoda
K
K
Anda
T
T
Nakamura
S
S
Yasunaga
A
A
Naito
S
S
Shibata
S
S
D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D008577:Meningeal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008579:Meningioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010641:Phenotype; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator