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.
|Low grade||143 ± 38||0.0069|
|High grade||173 ± 27|
|T1||124 ± 23||<0.0001|
|T4||178 ± 31|
|N0||125 ± 23||<0.0001|
|N1/N2||173 ± 35|
|M0||144 ± 33||0.0002|
|M1||195 ± 27|
|0/I||125 ± 24||<0.0001|
|III/IV||173 ± 34|