Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma.
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.
Yang
Guo-Fen
GF
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No, 651, Dongfeng Road East, 510060 Guangzhou, China.
He
Wei-Peng
WP
Cai
Mu-Yan
MY
He
Li-Ru
LR
Luo
Jun-Hang
JH
Deng
Hai-Xia
HX
Guan
Xin-Yuan
XY
Zeng
Mu-Sheng
MS
Zeng
Yi-Xin
YX
Xie
Dan
D
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063150:Polycomb Repressive Complex 1; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis
C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1