Immunohistochemical expression of stem cell markers CD44 and nestin in glioblastomas: Evaluation of their prognostic significance

Glioblastoma (GB) is a highly aggressive brain tumor with dismal prognosis and its standard of care consists of surgery followed by radiotherapy plus adjuvant chemotherapy with temozolomide (Stupp protocol). The response to therapy is variable and may be affected by the presence, within the tumor, of a proportion of cancer stem cells, implicated in chemo- and radioresistance. The expression of the stem cell markers nestin and CD44 in GBs has been extensively investigated.The aim of our study was to compare the immunohistochemical expression of nestin and CD44 in 25 cases of GBs and evaluate their possible prognostic value in relation to overall survival time.We found that their expression was strongly correlated (p = 0.0090 e r = 0.5320) and this finding was confirmed by observation with double staining techniques. For the first time, we made a separate immunohistochemical examination of membrane and cytoplasmic nestin staining, finding that although the two signals correlated (p = 0.0184, r = 0.4678), they had different impact on survival (respectively p = 0.0255 and p = 0.6376). Enhanced CD44 expression was associated with poor survival rates even if this finding was not statistically significant (p = 0.4481, ĸ2 = 0.5755).Overall, membrane nestin signal was found to be a valid prognostic factor. Furthermore, the detection of CD44 in GBs could be of value also as predictive marker; hyaluronan-based nanoparticles have already shown an active targeting of this antigen in other tumors.