Association of Stem Cell-Related Markers and Survival in Astrocytic Gliomas

Abstract

To study the clinical relevance of undifferentiated tumour cells in astrocytic gliomas we employed a large tumour tissue microarray (n=283) with corresponding clinical data and analyzed the expression of Nestin and Sox-2, which mark undifferentiated stem- and progenitor cells in the normal brain. Both markers were expressed abundantly and staining of nestin significantly increased with WHO grade. Further, nestin and Sox-2 immunoreactivity was significantly associated with tumour cell proliferation and nestin expression was independently associated with poor patient survival. Our findings suggest that immature glioma cells are involved in tumour growth and tumour progression and significantly impact on patient prognosis.

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

“…Many markers potentially specific for GSCs have been proposed such as A2B5 cell surface ganglioside epitope (A2B5) [26,27], aldehyde dehydrogenase (ALDH) [28], BMI1 polycomb ring finger oncogene (BMI1) [29,30], fucosyltransferase 4 (FUT4) (CD15) [31], Thy-1 cell surface antigen (Thy-1) (CD90) [32], prominin-1 (PROM1) (CD133) [5,6], chemokine (C-X-C motif) receptor 4 (CXCR4) [33], inhibitor of DNA binding 1 (ID1) [34], integrin α6 (ITGA6) [35], L1 cell adhesion molecule (L1CAM) [36], maternal embryonic leucine zipper kinase (MELK) [37], musashi-1 (msi1) [38], nestin (NES) [38][39][40], octamer-binding transcription factor 4 (OCT4) [41], OLIG2 [42] and SOX2 [38,[43][44][45]. 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].…”

Aberrant Expression of Retinoic Acid Signaling Molecules Influences Patient Survival in Astrocytic Gliomas

“…To this end, we resorted to a previously compiled data set generated with the same TMA, 27 which included expression analyses of the proliferation marker Ki-67, as well as the intermediate filament nestin and the transcription factor SOX2, two classical markers for immature cells of neoplastic and non-neoplastic origin. 28 -30 Correlation of staining frequencies with expression of RA signaling molecules in glioblastoma revealed a positive correlation of CRBP1 with Ki-67 ( ϭ 0.27, P Ͻ 0.001) and a positive correlation of nestin with FABP5 ( ϭ 0.23, P ϭ 0.003), both of which could be confirmed by double immunofluorescent staining ( Figure 6, A and B).…”

Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

“…The hypercellular and hyperproliferative zones of glioblastomas have the highest Sox2 expression. However, in other works the authors do not see any correlation between the degree of glioma malignancy and the survival term of patients and the Sox2 level [33,34], although they demonstrated increase of Sox2 expression in the glioma tissues compared to normal brain tissue. Thus of today there is no identical vision relative prognostic value of Sox2 at the gliomas.…”

“…There is no unanimous opinion in the literature regarding nestin expression. The majority of the investigators [29,30] demonstrated an increased nestin expression under an increased malignancy degree of the astrocytes and correlation between the level of nestin expression and the survival term of the patients with gliomas. K. J. Kim et al [31] did not established any statistically significant between the level of nestin expression, the malignancy degree of the astrocytes and survival term of the patients with brain gliomas.…”