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.
Int J Cancer. 2013 Feb 15;132(4):868-74. doi: 10.1002/ijc.27720. Epub 2012 Jul 30.
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.
迫切需要用于预测癌前口腔白斑（OL）中口腔癌发展的分子标志物。本研究的目的是检测癌症干细胞标志物 ALDH1 和 CD133 在 OL 患者样本中的表达模式，并确定其对随后发生口腔癌的预后价值。对经活检证实的 141 例 OL 患者的样本进行了 ALDH1 和 CD133 的免疫组织化学检测，这些患者的平均随访时间为 5.5 年。分析了患者的临床病理和随访数据。在 141 例 OL 患者中，分别有 54 例（38.3％）和 32 例（22.7％）观察到 ALDH1 和 CD133 的表达。Kaplan-Meier 分析显示，ALDH1 阳性患者中有 48.1％发生了口腔癌，而 ALDH1 阴性患者中则有 12.6％（p<0.001）。同时，CD133 阳性患者中有 59.4％发生了口腔癌，而 CD133 阴性患者中则有 16.5％（p<0.001）。多变量分析显示，ALDH1 和 CD133 的表达与 OL 转化的 4.17 倍（95％置信区间（CI），1.96-8.90；p<0.001）和 2.86 倍（95％CI，1.48-5.55；p=0.002）相关风险相关。总的来说，这些数据首次表明，在接受长期随访的大量 OL 患者中，ALDH1 和 CD133 的表达与恶性转化相关，这表明它们可能作为预测指标来识别具有高口腔癌发展风险的 OL。
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