[670] Expression of Cancer Stem Cell Regulators, Twist-1 and Bmi-1, in Colon Cancer: Implications for Their Oncogenic Role

Yusheng Han, Katherine Sun, Joseph Albanese, Jaya Sunkara, Aaron Leifer, Kathryn E Tanaka, Qiang Liu. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY

Background: Bmi-1 has been implicated in the modulation of self renewal in several types of stem cells. It has been demonstrated that Twist-1 directly regulates Bmi-1 to promote epithelial-mesenchymal transition and tumor initiating capability. Bmi-1 is required for full manifestation of increased self-renewal initiated by active β-catenin. The role and the interaction of Twist-1 and Bmi-1 in the progression and metastasis of colon cancer is unclear. We evaluated the expression of Bmi-1, Twist-1, β-catenin and E-cadherin in colon cancer to investigate the role of Twist-1 and Bmi-1 in the neoplasia progression sequence.
Design: Resections of colonic adenocarcinoma (23 stage 0/I, 27 stage III/IV) were stained by immunohistochemistry for Bmi-1, Twist-1, Beta-catenin and E-cadherin on paraffin embedded sections. The percentage (%) of epithelial cells was determined by a 0-3 scale. The total staining score was calculated by the sum of staining intensity multiplied by % to give a score range of 0-300.
Results: Bmi-1 nuclear expression was progressively increased in the colon carcinoma sequence compared to adjacent non-cancerous tissues: normal (25.2 ± 8.5), adenoma (102 ± 9.29), cancer (151 ± 38.1). High Bmi-1 nuclear expression was correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages.

Table 1. Correlation between Bmi-1 expression and the clinicopathologic features of colon cancer
 Bmi-1 expressionP-value
Histologic grade  
Low grade143 ± 380.0069
High grade173 ± 27 
T Classfication  
T1124 ± 23<0.0001
T4178 ± 31 
N Classification  
N0125 ± 23<0.0001
N1/N2173 ± 35 
M Classificantion  
M0144 ± 330.0002
M1195 ± 27 
Clinical Stage  
0/I125 ± 24<0.0001
III/IV173 ± 34 

Although Twist-1 expression showed no significant stage difference, it was relatively increased at the invasive tumor front in all stages as compared with the tumor center (P<0.01). At the invasive tumor front, there were increased nuclear expression of Bmi-1, Twist-1 and β-catenin, and decreased expression of membranous and cytoplasmic E-cadherin. Nuclear expression of β-catenin was less in stage 0/I adenocarcinomas compared to stage III/IV (p <0.01).
Conclusions: Bmi-1 and Twist-1 may be crucial for invasion and metastasis in colon cancer as their expresion was increased at the invasive tumor front and Bmi-1 expression was correlated with advanced clinical stage. Bmi-1 may also play a critical role in the pathogenesis of colon cancer as it showed increasing expression along the colon cancer progression sequence.
Category: Gastrointestinal

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 100, Monday Morning


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