The Expression Status and Prognostic Value of Cancer Stem Cell Biomarker CD133 in Cutaneous Squamous Cell Carcinoma

Rui Xu, Mu-Yan Cai, Rong-Zhen Luo, Xin Tian, Jian-de Han, Mu-Kai Chen
JAMA Dermatology 2016, 152 (3): 305-11

IMPORTANCE: The CD133 protein has been considered a key biomarker of cancer stem cells in various cancers. However, the expression status and prognostic significance of CD133 in cutaneous squamous cell carcinoma (cSCC) are poorly understood.

OBJECTIVE: To investigate the expression of cancer stem cell biomarker CD133 in cSCC tissue and its effect on clinicopathological features and outcomes in patients with cSCC.

DESIGN, SETTING, AND PARTICIPANTS: Immunohistochemistry was performed on a tissue microarray to investigate the expression levels of CD133 in cSCC tissue. Receiver operating characteristic curve analysis, Kaplan-Meier plots, and a Cox proportional hazards regression model were applied to analyze the data. Samples were obtained from the archives of the First Affiliated Hospital, Sun Yat-Sen University Cancer Center, and Guangzhou Institute of Dermatology and Venerology. In total, 165 paraffin-embedded clinicopathological samples from 165 patients were obtained from the archives of hospitals between June 1, 1996, and December 31, 2010. Follow-up data were available for these cases.

MAIN OUTCOMES AND MEASURES: The CD133 expression in cSCC tissue, correlation of CD133 expression with clinicopathological features of cSCC, and association of CD133 expression with prognosis in patients with cSCC.

RESULTS: Based on the receiver operating characteristic curves, the cutoff value for high CD133 expression was defined as greater than 65% of tumor cells positively stained. High CD133 expression was observed in 50.9% (84 of 165) of the cSCC samples and in 16.7% (5 of 30) of adjacent nonmalignant epithelial tissue samples (P = .001). High CD133 expression was positively correlated with poorly differentiated cSCC (48.0% [73 of 84] for well to moderately differentiated vs 84.6% [11 of 84] for poorly differentiated, P = .01) and with advanced tumor stage (45.5% [55 of 84] for stage I-II vs 65.9% [29 of 84] for stage III, P = .02). In univariable survival analysis, high CD133 expression was correlated with poor prognosis (mean survival, 63.4 vs 95.7 months; P < .001). In multivariable analysis, CD133 expression was an independent prognostic factor for cSCC (hazard ratio, 1.9152; 95% CI, 1.1950-3.3495; P = .02).

CONCLUSIONS AND RELEVANCE: High CD133 expression is associated with poorly differentiated and advanced-stage cSCC. High CD133 expression was also correlated with poor prognosis in patients with cSCC. It may serve as a useful biomarker to predict prognosis in patients with cSCC.

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