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Original Investigation
March 2016

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

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

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.