Increased expression of avian erythroblastosis virus E26 oncogene homolog 1 in World Health Organization grade 1 meningiomas is associated with an elevated risk of recurrence and is correlated with the expression of its target genes matrix metalloproteinase-2 and MMP-9.
BACKGROUND
The transcription factor avian erythroblastosis virus E26 (V-Ets) oncogene homolog 1 (Ets-1) is involved in tumor development and progression through the transcriptional regulation of several matrix-degrading enzyme systems, including matrix metalloproteinases (MMPs). It has been demonstrated that the MMPs are expressed strongly in high-grade meningiomas. To determine the biologic significance of Ets-1 in the progression of benign meningiomas, the authors investigated the expressions of Ets-1 and its target genes MMP-2 and MMP-9 in primary and recurrent, Grade 1 meningiomas.


METHODS
The expression levels of Ets-1, MMP-2, and MMP-9 were examined by immunohistochemistry in 70 Grade 1 meningiomas, including 36 primary tumors without recurrence after 5 years of follow-up and 17 pairs of primary tumors and subsequent recurrences.


RESULTS
The results demonstrated higher expression of Ets-1, MMP-2, and MMP-9 proteins in meningiomas with subsequent recurrences compared with meningiomas from patients who had no recurrences (P < .001). In addition, Ets-1 expression was correlated with the expression of both MMP-2 and MMP-9.


CONCLUSIONS
Ets-1 may be involved in meningioma recurrence by up-regulating MMP-2 and MMP-9. Increased expression of these genes in World Health Organization grade 1 meningiomas may serve as an indicator for a high risk of recurrence.
Okuducu
Ali Fuat
AF
Institute of Neuropathology, Charite-Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. a-f.okuducu@charite.de
Zils
Ulrich
U
Michaelis
Silke A M
SA
Mawrin
Christian
C
von Deimling
Andreas
A
D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis*; D012307:Risk Factors; D014944:World Health Organization
D050784:Proto-Oncogene Protein c-ets-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9