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

Abstract

BackgroundIt 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.MethodsThe 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.ResultsIntensive 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).ConclusionsThese 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.

BMI-1, a promising therapeutic target for human cancer

“…Overexpression of BMI-1 has been previously reported in gastric, ovarian, breast, head and neck, pancreatic and lung cancer, as well as in primary hepatocellular carcinoma (HCC) and endometrial carcinoma (8)(9)(10)(11)(12)(13)(14)(15)(16). In addition, BMI-1 overexpression has been identified in patients suffering from myelodysplastic syndrome, chronic myeloid leukemia, acute myeloid leukemia and lymphoma (17)(18)(19)(20).…”

“…Drug resistance is an important cause of cancer treatment failure and previous studies have demonstrated that the overexpression of BMI-1 was associated with cancer chemosensitivity (Table I) (9,30,31). Certain in vitro studies revealed that overexpression of BMI-1 can promote chemoresistance (23), whereas depletion of BMI-1 is able to enhance the chemosensitivity of HCC (15,37) and ovarian cancer cells (38,39).…”

“…For instance, Song et al investigated the survival of 72 patients with pancreatic cancer and identified that the overexpression of BMI-1 was associated with a significantly reduced overall survival (24). In addition, Yang et al studied the BMI-1 expression and survival in a cohort of 179 patients with invasive ovarian carcinoma (9). The authors demonstrated a significant association between increased BMI-1 expression and reduced patient survival (mean, 49 months), when compared with patients presenting a low BMI-1 expression (mean, 100 months; P<0.001) (9).…”

“…In addition, Yang et al studied the BMI-1 expression and survival in a cohort of 179 patients with invasive ovarian carcinoma (9). The authors demonstrated a significant association between increased BMI-1 expression and reduced patient survival (mean, 49 months), when compared with patients presenting a low BMI-1 expression (mean, 100 months; P<0.001) (9). Furthermore, Vrzalikova et al performed immunohistochemical staining for BMI-1 in 179 NSCLC samples, identifying that the five-year survival rate of BMI-1-positive patients was only 31.2%, in contrast to BMI-1-negative patients that exhibited a survival rate of 50.7% (P=0.004) (43).…”

Prognostic role of the cancer stem cell marker CD44 in ovarian cancer: a meta-analysis

“…Several studies have shown that CSC-related factors, including ALDH1, CD133, and Bmi-1, are involved in promoting ovarian cancer progression (Chang et al, 2009;Yang et al, 2010;Silva et al, 2011). In addition, CSCs exhibit remarkable phenotypic and functional heterogeneities, which may help to distinguish them from non-stem cancer cells and provide a potential therapeutic target for the development of anticancer therapies to improve clinical outcomes (Tang, 2012).…”