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faculty: "FNWI" and publication year: "2008"
| Authors||I.B. Engelsen, M. Mannelqvist, I.M. Stefansson, S.L. Carter, R. Beroukhim, A.M. Øyan, A.P. Otte, K.H. Kalland, L.A. Akslen, H.B. Salvesen|
|Title||Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma|
|Journal||BRIT J CANCER|
|Faculty||Faculty of Science|
|Institute/dept.||FNWI: Swammerdam Institute for Life Sciences (SILS)|
|Abstract||We studied the expression of polycomb group (PcG) protein BMI-1 in a large population-based patient series of endometrial carcinomas in relation to clinical and molecular phenotype. Also, 57 fresh frozen endometrial carcinomas were studied for the relationship between BMI-1 protein expression, BMI-1 mRNA level, and activation of an 11-gene signature reported to represent a BMI-1-driven pathway. BMI-1 protein expression was significantly weaker in tumours with vascular invasion (P<0.0001), deep myometrial infiltration (P=0.004), and loss of oestrogen receptor (ER) (P<0.0001) and progesterone receptors (PR) (P=0.03). Low BMI-1 protein expression was highly associated with low BMI-1 mRNA expression (P=0.002), and similarly low BMI-1 mRNA expression correlated significantly with vascular invasion, ER and PR loss, and histologic grade 3. In contrast, activation of the reported 11-gene signature, supposed to represent a BMI-1-driven pathway, correlated with low mRNA expression of BMI-1 (P<0.001), hormone receptor loss, presence of vascular invasion, and poor prognosis. We conclude that BMI-1 protein and mRNA expression are significantly correlated and that BMI-1 expression is inversely associated with activation of the 11-gene signature. Loss of BMI-1 seems to be associated with an aggressive phenotype in endometrial carcinomas.|
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