Prognostic impact of CD133 expression as a tumor-initiating cell marker in endometrial cancer☆

Summary 

Tumor-initiating cells are known to be the major source of tumor propagation and might be an attractive therapeutic target. The present study dissected the roles of CD133 as a tumor-initiating cell marker in endometrial cancer and investigated the prognostic impact of this marker expression. Flow cytometry using 6 endometrial cancer cell lines revealed that the frequency of CD133⁺ cells varied widely among the cell types and that Ishikawa and MFE280 cells contained significantly higher ratio (10%-20%) of such cells; therefore, these were subjected to the subsequent analyses. Sorted CD133⁺ cells showed more aggressive proliferative potential in vitro and more increased tumorigenicity in nude or NOD/SCID mice than CD133⁻ cells and generated both CD133⁺ and CD133⁻ cells. Furthermore, they showed apparent resistance to cisplatin- or paclitaxel-induced cytotoxicity compared with CD133⁻ cells. CD133⁺ cells had a greater S-phase fraction than CD133⁻ cells, and the serum starvation that induced G0/G1 accumulation decreased the population of CD133⁺ cells. Finally, we immunohistochemically analyzed the CD133 expression in endometrial cancer specimens from 62 patients. CD133 expression was not significantly associated with any of the clinicopathologic characteristic of tumors. However, the Kaplan-Meier analysis revealed that tumors with high CD133 expression showed worse overall survival (P = .023, log-rank test) than those with low CD133 expression; and the Cox regression hazard model found that high CD133 expression was an independent prognostic factor (P = .045). Thus, the present study demonstrates that CD133 is not only a tumor-initiating cell marker but also a critical prognostic marker in endometrial cancer.

Keywords: Endometrial cancer, Tumor-initiating cell, CD133, Prognostic factor