Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma

BMC Cancer. 2010 Apr 8:10:133. doi: 10.1186/1471-2407-10-133.

Abstract

Background: It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear.

Methods: The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas.

Results: Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005).

Conclusions: These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Female
  • Gene Amplification
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Polycomb Repressive Complex 1
  • Prognosis
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Treatment Outcome
  • Tumor Suppressor Protein p14ARF / biosynthesis

Substances

  • BMI1 protein, human
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Tumor Suppressor Protein p14ARF
  • Polycomb Repressive Complex 1