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 5 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.Head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC), is the sixth most common type of malignancy worldwide; early diagnosis of high-risk potentially malignant lesion is a high priority for reducing both morbidity and mortality. 1-3 Increasing evidence indicates that the initiation, progression, recurrence and metastasis of HNSCC are related to the behavior of a small subpopulation of cancer stem cells (CSCs). [4][5][6] Clinical and therapeutic implications of CSCs has attracted growing attention, including early detection and prognostication of cancer. In addition, CSCs can be identified and isolated by expression of distinctive markers to enrich for stem cells. 7 Oral leukoplakia (OL) is the best-known potentially malignant disorder of OSCC, with a frequency of malignant transformation between 17% and 35%. 8,9 Histologic grading of epithelial dysplasia currently is the most important indicator for determining the risk of OL transformation; however, it is a well-known fact that this histologic classification is insufficient and may involve subjectivity. 10 Furthermore, previous studies have demonstrated no evidence of an effective treatment to prevent malignant transformation; it is increasingly evident that the identification of high-risk OL before transformation is of utmost importance for effective intervention. 11 Therefore, novel biomarkers are required to identify the OL lesions at a higher risk for transformation, which may provide opportunities for prophylactic interventio...
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