Yang et al. BMC Cancer 2010, 10:133 http://www.biomedcentral.com/1471-2407/10/133 R E S E A R C H A R T I C L E Open Access Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma Guo-Fen Yang1,2, Wei-Peng He2, Mu-Yan Cai1, Li-Ru He1, Jun-Hang Luo2, Hai-Xia Deng1, Xin-Yuan Guan1, Mu-Sheng Zeng1, Yi-Xin Zeng1, Dan Xie1* 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. Background Ovarian cancer is a major lethal gynecological malig- nancy worldwide [1]. Its peak incidence is at the age 45 or above. Because of its insidious onset, approximately 70% of ovarian cancer patients were diagnosed at advanced stage(FIGO III/IV stage) with a very poor prognosis, whose 5-year survival rate is of <30% [2]. Ovarian carcinoma is the most common histopathologi- cal type of ovarian cancer. The development and pro- gression of ovarian carcinoma are presumed to be a multi-step process involving multiple genetic changes [3]. Thus, a substantial amount of research on ovarian carcinoma has focused on the discovery of specific * Correspondence: xied@mail.sysu.edu.cn 1State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat- Sen University, No. 651, Dongfeng Road East, 510060 Guangzhou, China molecular markers that are present in ovarian carcinoma cells which could serve as reliable prognostic factors. The B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene belongs to mammalian Polycomb- group (PcG) family forming multimeric gene-repressing complexes involved in axial patterning, hematopoiesis, regulation of proliferation, and senescence. Bmi-1 was first identified as a proto-oncogene that cooperated with c-Myc in generating pre-B-cell lymphomas in a murine model [4-8]. It has been discovered that Bmi-1 partici- pates in cell cycle regulation by acting as a stable tran- scriptional repressor of the Ink4a locus, which encodes the tumor suppressor proteins p16Ink4a and p19Arf (mouse homologue of human p14ARF). Inactivation of the p16Ink4a-pRb pathway and p14ARF-MDM2-p53 pathway by Bmi-1 deregulation has been clearly © 2010 Yang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.