Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma

• Published in: British journal of cancer Vol. 98; no. 10; pp. 1662 - 1669
• Main Authors: ENGELSEN, I. B, MANNELQVIST, M, STEFANSSON, I. M, CARTER, S. L, BEROUKHIM, R, OYAN, A. M, OTTE, A. P, KALLAND, K. H, AKSLEN, L. A, SALVESEN, H. B
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 20.05.2008
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer research; Correspondence; Cyclin-dependent kinases; Endometrial cancer; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Gynecology; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Kinases; Medical prognosis; Medical research; Medical sciences; Middle Aged; Molecular Diagnostics; Neoplasm Invasiveness; Neoplasm Staging; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Obstetrics; Patients; Phenotype; Polycomb Repressive Complex 1; Polymerase Chain Reaction; Protein Array Analysis; Protein expression; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA, Messenger - metabolism; Stem cells; Survival Analysis; Tumors; Vascular Neoplasms - metabolism; Vascular Neoplasms - pathology; United States > US; Norway; Immunohistochemistry; Endometrium cancer; BMI-1; gene signature; endometrial carcinoma; mRNA; Malignant tumor; Metastasis; Invasion; Female genital diseases; Gene expression profile; Anatomic pathology; Cancerology; Messenger RNA; BMI1 gene; C-Onc gene; Blood vessel; Uterine diseases; Circulatory system; Endometrium carcinoma; hormone receptors; Protooncogene; Cancer; Hormonal receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604360

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.