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

Br J Cancer. 2008 May 20;98(10):1662-9. doi: 10.1038/sj.bjc.6604360. Epub 2008 May 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Polycomb Repressive Complex 1
  • Polymerase Chain Reaction
  • Protein Array Analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Survival Analysis
  • Vascular Neoplasms / metabolism*
  • Vascular Neoplasms / pathology*

Substances

  • BMI1 protein, human
  • Biomarkers, Tumor
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Repressor Proteins
  • Polycomb Repressive Complex 1