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Original Investigation |

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

Rui Xu, BS1; Mu-Yan Cai, MD2; Rong-Zhen Luo, MD2; Xin Tian, MD3; Jian-de Han, MD1; Mu-Kai Chen, MD1
[+] Author Affiliations
1Department of Dermatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
2Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China
3Department of Dermatology, Guangzhou Institute of Dermatology and Venerology, Guangzhou, China
JAMA Dermatol. 2016;152(3):305-311. doi:10.1001/jamadermatol.2015.3781.
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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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Figure 1.
Receiver Operating Characteristic Curve Analysis to Determine the Cutoff Value for High CD133 Expression

The sensitivity and 1−specificity for each outcome are plotted. AUC indicates area under the curve.

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Figure 2.
CD133 Expression in Cutaneous Squamous Cell Carcinoma Tissue and Adjacent Nonmalignant Epithelial Tissue by Immunohistochemistry

The top panels show original magnification ×100. A, High CD133 expression is observed in a case in which more than 90% of tumor cells revealed positive immunostaining of CD133 in their membrane and cytoplasm. B, A second case demonstrates low CD133 expression in which less than 30% of tumor cells revealed positive immunostaining of CD133 in their membrane and cytoplasm. C, Almost no CD133 expression is shown in a third case. D, Adjacent nonmalignant epithelial tissue shows almost no CD133 expression. The bottom panels show original magnification ×400 of the insets.

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Figure 3.
Kaplan-Meier Survival Analysis of CD133 Expression in Patients With Cutaneous Squamous Cell Carcinoma

The numbers at risk are 81 with low expression and 84 with high expression. A, Total probability of recurrence-free survival is shown. B, Total probability of overall survival is shown.

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