Expression patterns of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation of oral leukoplakia*

Authors

  • Wei Liu,

    1. Department of Oral Maxillofacial–Head and Neck Oncology, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    Search for more papers by this author
    • *

      W.L., L.W. and X.-M.S. contributed equally to this work.

  • Lan Wu,

    1. Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    Search for more papers by this author
    • *

      W.L., L.W. and X.-M.S. contributed equally to this work.

  • Xue-Min Shen,

    1. Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    Search for more papers by this author
    • *

      W.L., L.W. and X.-M.S. contributed equally to this work.

  • Lin-Jun Shi,

    1. Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    Search for more papers by this author
  • Chen-Ping Zhang,

    1. Department of Oral Maxillofacial–Head and Neck Oncology, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    Search for more papers by this author
  • Li-Qun Xu,

    Corresponding author
    1. Department of Oral Maxillofacial–Head and Neck Oncology, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    • Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China
    Search for more papers by this author
    • Tel.: +86-21-2327-1699, Fax: +86-21-6308-7076

  • Zeng-Tong Zhou

    Corresponding author
    1. Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
    • Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China
    Search for more papers by this author
    • Tel.: +86-21-2327-1699, Fax: +86-21-6308-7076


Abstract

Molecular markers for predicting oral cancer development in premalignant oral leukoplakia (OL) are urgently needed. The objective of this study was to examine the expression patterns of cancer stem cell markers ALDH1 and CD133 in samples from patients with OL, and determine their prognostic values for subsequent development of oral cancer. Immunohistochemistry for ALDH1 and CD133 was performed in samples from a cohort of 141 patients with biopsy-proven OL who received a mean follow-up of 5.5 years. Patient clinicopathologic and follow-up data were analyzed. Expression of ALDH1 and CD133 was observed in 54 (38.3%) and 32 (22.7%) of 141 patients with OL, respectively. Kaplan–Meier analysis showed that 48.1% patients with ALDH1-positivity developed oral cancer compared with 12.6% those with ALDH1-negativity (p < 0.001). Meanwhile, 59.4% patients with CD133-positivity developed oral cancer compared with 16.5% those with CD133-negativity (p < 0.001). Multivariate analysis revealed that ALDH1 and CD133 expression was associated with 4.17-fold [95% confidence interval (CI), 1.96–8.90; p < 0.001] and 2.86-fold (95% CI, 1.48-5.55; p = 0.002) increased risk of OL transformation, respectively. Collectively, these data demonstrated for the first time that the expression of ALDH1 and CD133 correlated with malignant transformation in a large series of patients with OL who received a long-term follow-up, which suggests that they may serve as predictors to identify OL with a high risk of oral cancer development.

Ancillary