Analysis of Clinical Prognostic Significance of Cancer Stem Cell Markers in Patients with Papillary Thyroid Carcinoma

Abstract

Introduction: Recently, the cancer stem cells (CSCs) model was new era of excitement in thyroid cancer research, which indicates that a small subset of CSCs existed in tumor cells may contribute to the initiation, progression and recurrence of metastatic disease, as well as therapy resistance. The aim of this study was to evaluated presence of CD44, CD24 and CD133 tumor cells in papillary thyroid carcinoma (PTC) as marker of aggressiveness and poor prognosis. Methods: All patients with PTC, who underwent successful surgical resections from January 2003 to December 2012 in single tertiary hospital, were included in this study. Tissue arrays were made with 454 primary tumor tissues. Immunohistochemistry(IHC) of 3 cancer stem cell markers (CD24, CD44 and CD133) were applied to corresponding tissue arrays. IHC was graded by semiquantative histologic scoring considering the extent and intensity of the staining. IHC results were correlated with clinicopathological characteristics and with recurrence free survival. Results: In total 500 patients, 46 cases were recurred during 70 month median follow-up period. In univariate log rank test of Kaplan Meier survival model, sex (p = 0.010), age (p = 0.005), cN1b (p = 0.000), pN1 > 5 (p = 0.000), pTumor size > 2 cm (p = 0.000), extrathyroidal extension (p = 0.000), CD24 (-) (p = 0.000) were prognostic factors for RFS. CSCs marker combinations such as CD44 (+)/CD24 (-), CD24 (-)/CD133 (+), CD44 (+)/CD24 (-)/CD133 (+) also showed statistically significant in Log Rank test. Conclusion: Expression of CSC markers CD44 (+), CD24 (-), and CD133 (+) in tissue samples of PTC correlates with RFS. In particular, the combination of CD44 (+) and CD24 (-) showed a statistically significant relationship with RFS and a strong correlation with gross extrathyroidal extension.