Lack of Prognostic Significance of Survivin in Pediatric Medulloblastoma

Abstract

Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children. Because of the significant rate of mortality and treatment-related morbidity, the identification of prognostic factors could lead to a more accurate selection of patients who can benefit from a less aggressive therapy and improve risk stratification. Survivin is an inhibitor of apoptosis protein (IAP), the expression of which has been associated with worse prognosis in MDB. However, both of its subcellular localizations may contribute to tumor progression, and ultimately, survivin subcellular localization prognostic value depends on tumor type biological features. The goal of this study was to analyze these survivin features in the pediatric MDB tumor samples and its impact on clinical outcome. Survivin expression and subcellular localization were accessed by immunohistochemistry in a series of 41 tumor samples. Kaplan-Meier survival curves were compared using the log-rank test. Survivin expression ranged from completely absent to fully present in a notably higher pattern of nuclear localization than cytoplasmic (19 of 41 versus 4 of 41, respectively). However, survivin expression and subcellular localization were not associated with five-year overall survival or metastasis status at diagnosis, which was the only statistically significant prognostic factor in our series (p = 0.008). Taken together, our results suggest that survivin expression should be further studied in large, multicenter series to determine its accurate impact on prognosis and pathobiology of pediatric MDB.

Prognostic role of survivin in patients with glioma

“…[ 6 – 8 ] Survivin is expressed during the G 2 /M phase of the cell cycle, [ 29 ] and its expression has been detected in both the nuclei and cytoplasm of tumor cells. [ 15 ] In the nuclei, it is crucial to promote accurate mitosis progression. [ 30 ] In the cytoplasm, it suppresses apoptosis via the direct inhibition of caspase-associated proteins.…”

“…Although most studies demonstrated that overexpression of survivin was associated with worse prognosis in glioma, [ 12 – 14 ] some researchers found no significant association between survivin and survival. [ 15 , 16 ] Due to the inconsistency, we aimed to systematically evaluate the prognostic role of survivin in patients with glioma through performing a meta-analysis.…”

Imatinib increases apoptosis index through modulation of survivin subcellular localization in the blast phase of CML cells

“…In agreement with this, a possible limitation of our study could be the fact that the commercial polyclonal antibody used in our immunocytochemistry assay cannot distinguish survivin isoforms. Instead, this antibody has been shown adequate in assessing total survivin expression [38,39]. However, it is interesting to note that, through Western blot analysis there was significant positive correlation with the mRNA positivity of survivin standard, survivin-Ex3, survivin-2B and survivin-2a.…”

FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance

“…For XIAP, Survivin, FOXM1 and Her2 staining, IHC was performed on consecutive 3 µm sections as described previously (Faccion et al, 2011). Detailed information can be found …”