The presence of stem cell marker‐expressing cells is not prognostically significant in glioblastomas

Abstract

Glioblastoma is one of the most frequent primary brain tumors and is characterized by aggressive clinical behavior and biologic heterogeneity. To evaluate the prognostic implication of cancer stem cell markers in glioblastoma, the expression of these markers was investigated in a large series of glioblastoma patients in relation to the survival rate. This series includes 88 cases of glioblastoma that were diagnosed at the Chonnam University Hwasun Hospital from 2004 to 2009. The expression of newly established stem cell markers (nestin, CD133 and CD15) was detected using immunohistochemical analysis. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients' survival data. The expression of nestin was high in 60 cases (68.2%). CD133 and CD15 were positive in 52 cases (59.1%) and 40 cases (45.5%), respectively. No statistically significant difference in patient survival according to stem cell marker expression was observed (P > 0.05). However, gross total resection or combined radiation therapy and chemotherapy significantly prolonged survival (P = 0.04 and P = 0.04). Cox's proportional hazards model showed that the gross total resection and combined radiation therapy and chemotherapy were independent prognostic factors. Although the correlation of stem cell marker expression with clinical outcome in glioma is of considerable interest, the data do not support their prognostic value in glioblastoma. Identification of the key cells in the glioblastoma population in the context of clinical outcomes will provide insight into the mechanism of brain tumorigenesis and will be of paramount importance in determining therapeutically appropriate targets.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…Among these, much attention has been given to CD133, which is currently used to identify and isolate GSCs [40,43,[46][47][48][49][50]. Despite the fact that this is the most widely used antigen for enrichment of GSCs, there are several arguments to suggest the existence of CD133-negative GSCs: CD133 is not detectable in many fresh GBM specimens [14,31,51], and some studies revealed CD133-negative GBM cultures with the ability to self-renew and to form tumours in xenotransplantation assays [14,51,52].…”

Nestin expression in high-grade osteosarcomas and its clinical significance

“…Several authors (27,37,49,51) showed that nestin expression correlates with advanced-grade gliomas; additionally, some researchers also demonstrated a statistically significant correlation between nestin expression and poor prognosis in glioma patients (27,37,51). Surprisingly, no prognostic implications of nestin expression were found in glioblastoma multiforme, i.e., in the most malignant form of astrocytoma (52,53). In contrast, correlations between nestin expression and poorer clinical outcomes were documented in malignant melanoma (54), hepatocellular carcinoma (55), non-small cell lung carcinoma (56), gastric carcinoma (33) and prostate cancer (35).…”

Cancer stem cells: The potential role of autophagy, proteolysis, and cathepsins in glioblastoma stem cells

“…116,117 Glioblastoma stem cells are suggested to emerge from neural stem cells or partially from differentiated progenitor cells and are characterized by stem cell markers, such as Sox-2, Nestin, Musashi, and the disputed CD133. However, the latter certainly does not identify the most stem cell-like population in glioblastoma, 118,119 and recent work of Schneider et al 28 shows that a high-level state of plasticity exists between the stem cell and differentiated phenotypes. Nevertheless, glioblastoma stem cells are highly resistant to treatment, partially due to the high expression of the multidrug resistance ABC transporter protein breakpoint cluster region pseudogene 1 (BCRP1), DNA repair proteins, and gene products that inhibit apoptosis.…”