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

• Published in: Human pathology 2010-11, Vol.41 (11), p.1516-1529
• Main Authors: Nakamura, Mitsuhiro, MD, PhD, Kyo, Satoru, MD, PhD, Zhang, Bo, MD, Zhang, Xiuzhi, MD, Mizumoto, Yasunari, MD, PhD, Takakura, Masahiro, MD, PhD, Maida, Yoshiko, MD, PhD, Mori, Noriko, MD, PhD, Hashimoto, Manabu, MD, Ohno, Satoshi, MD, PhD, Inoue, Masaki, MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cancer therapies; Carcinoma, Endometrioid - metabolism; Carcinoma, Endometrioid - mortality; Carcinoma, Endometrioid - pathology; Carcinoma, Endometrioid - therapy; CD133; Cell culture; Cell cycle; Cell Line, Tumor; Cell Proliferation; Cloning; Combined Modality Therapy; Endometrial cancer; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Endometrial Neoplasms - therapy; Female; Female genital diseases; Flow Cytometry; Gynecology. Andrology. Obstetrics; Humans; Investigative techniques, diagnostic techniques (general aspects); Japan - epidemiology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Middle Aged; Molecular weight; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase chain reaction; Prognosis; Prognostic factor; Proteins; Receptors, OX40 - metabolism; Stem cells; Survival Rate; Tumor Stem Cell Assay; Tumor-initiating cell; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2010.05.006

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.