Relationship Between Cancer Stem Cell Markers (CD24, 44, 133) and Postoperative Prognosis of Oral Squamous Cell Carcinoma

Abstract

Introduction: Many studies have focused on the prognostic roles of cancer stem cell markers, but the results remain unclear. CD44 is the most well-known cancer stem cell marker in head and neck cancers, and CD24 and CD133 are representative cancer stem cell markers in many solid tumors. The aim of this study was to gain insight into the relationships between expression of CD24, CD44, and CD133, either alone or in combination, and prognostic parameters of oral squamous cell carcinoma (OSCC).

Methods: Patients with OSCC who underwent successful surgical resection from January 2003 to December 2011 in a single tertiary hospital were included in this study. Tissue arrays composed of 67 primary tumor tissues were generated and used for immunohistochemistry (IHC) against CD24, CD44, and CD133. IHC was graded by a semiquantitative histologic scoring system (H score) that considered the extent and intensity of the staining. IHC results were correlated with clinicopathological characteristics and with clinical outcomes such as relapse-free, disease-free, and overall survivals.

Results: In the 67 cases, the oral tongue was the most frequently affected primary site (56.7%). In tumor-lymph node-metastasis (TNM) staging, stage IV (34.3%) was most frequent, followed by stages I (26.9%), II (25.4%), and III (13.4%). Despite successful resection, there was 28.3% recurrence. TNM stage IV was highly related with the recurrence rate (p = 0.002). None of the 3 cancer stem cell markers (CD24, CD44, and CD133) had a statistically significant relationship with lymph node metastasis, TNM stage, or microscopic invasion into adjacent tissues. High expression of CD44 alone was associated with relapse-free survival (p=0.049), as were combined high expression of CD44 and CD133 (p=0.046) and CD44 and CD24 (p=0.015). CD44 expression also tended towards correlation with disease-free survival

however, this was not statistically significant (p=0.071).

Conclusions: Overall, the expression of CD44 had the strongest correlation with tumor recurrence. Additionally, when CD44 expression was combined with CD24 expression, CD24+CD44+ patients had the poorest chance of relapse-free survival. Thus, CD44 expression alone, and also in combination with CD24, should be considered when evaluating the prognosis for relapse-free survival of OSCC.