Association Between CD133, CD44, and Nestin Expression and Prognostic Factors in High-Grade Meningioma

Abstract

Meningioma is the most common primary brain tumor. It is graded as I, II, or III based on the World Health Organization (WHO) classification of central nervous system tumors. Meningiomas, especially those classified as grade II-III, have an aggressive history and a high recurrence rate. Cancer stem cells (CSCs) represent a small subset of tumor cells and are considered to be involved in tumor initiation, growth, and/or recurrence. To date, the CSCs of meningioma have not been well established. We assessed 51 grade II/III meningiomas using immunohistochemistry to determine if a correlation exists with the prognosis by investigating CD133, CD44, and nestin expression as possible CSC markers and age, gender, initial WHO tumor grade, Simpson grade, and the use of adjuvant radiation therapy. The median overall survival was 7.1 years, and the median progression-free survival (PFS) was 1.8 years. Univariate analysis using Cox proportional hazards regression revealed a negative correlation between CD133 and nestin expression and PFS (P= 0.0176 and P= 0.0138, respectively), and high expression of CD44 demonstrated a tendency toward a shorter PFS (P= 0.0563), as did the initial WHO grade and Simpson grade found at the initial operation (P= 0.0166 and P 0.0333, respectively). Multivariate analysis showed relevance between CD133 and nestin expression and PFS. CD133 and nestin expression, initial WHO grade and Simpson grade were associated with PFS in patients with grade II/III meningioma. These findings might suggest that these molecules are representative of CSCs in meningioma regarding the aspect of clinical course.