Clinical prognostic significance of cancer stem cell markers in patients with papillary thyroid carcinoma

The recent development of the cancer stem cell (CSC) model has been heralded as a new era in thyroid cancer research. The aim of this study was to evaluate the presence of CD44(+) and CD24(−) tumor cells in papillary thyroid carcinoma (PTC) as markers of aggressiveness and poor prognosis. Patients with PTC, who underwent successful surgical resections between January 2003 and December 2012 at a single tertiary hospital, were included in this study. Tissue arrays were prepared from 454 primary tumor tissues. Immunohistochemistry (IHC) was performed to detect the CSC markers CD24 and CD44 on the tissue arrays. IHC was graded using a semi-quantitative histology scoring system based on the extent and intensity of staining. Subsequently, the association between IHC results and clinicopathological characteristics and recurrence-free survival (RFS) was analyzed. In 454 patients, 39 cases recurred during the 70-month median follow-up period, with some patients exhibiting multiple sites of relapse. The results of a Kaplan-Meier survival analysis and univariate log-rank test demonstrated that sex (P=0.008), age (P=0.002), cN1b, defined as metastasis to unilateral, bilateral, or contralateral neck lymph nodes or retropharyngeal lymph nodes (P<0.001), pN1, defined as pathologically proven lymph node metastasis >5 (P<0.001), tumor size >2 cm (P<0.001), extrathyroidal extension (P=0.001) and CD24(−) (P<0.001) were prognostic factors for RFS. CSC marker combinations (CD44(+)/CD24(−)) also exhibited statistical significance in the log-rank test. In conclusion, expression of the CSC markers CD44(+) and CD24(−) in PTC tissue samples was associated with RFS. The combination of CD44(+) and CD24(−) exhibited a statistically significant negative association with RFS and a strong association with gross extra-thyroidal extension.