1. ¹Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen 5021, Norway
2. ²The Gade Institute, University of Bergen, Postboks 7800, Bergen 5020, Norway
3. ³Institute of Clinical Medicine, University of Bergen, Postboks 7800, Bergen 5020, Norway
4. ⁴Department of Pathology, Haukeland University Hospital, Bergen 5021, Norway
5. ⁵The Harvard MIT Division of Health Sciences and Technology, Boston, MA, USA
6. ⁶Broad Institute of Harvard and MIT, Boston, MA, USA
7. ⁷Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
8. ⁸Department of Microbiology and Immunology, Haukeland University Hospital, Bergen 5021, Norway
9. ⁹Department of Biochemistry, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

Correspondence: Dr IB Engelsen, Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen 5021, Norway. E-mail: ingeborg.engelsen@helse-bergen.no

Received 2 January 2008; Revised 14 March 2008; Accepted 26 March 2008; Published online 13 May 2008.

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.