Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome - PubMed (original) (raw)
Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome
J R Fangusaro et al. Br J Cancer. 2005.
Abstract
Survivin is an apoptotic inhibitor that is expressed at high levels in a variety of malignancies. Survivin has four known alternative splice forms (Survivin, Survivin-2B, Survivin-deltaEx3, and Survivin-3B), and the recent literature suggests that these splice variants have unique functions and subcellular localisation patterns. We evaluated 19 fresh-frozen paediatric medulloblastomas for the expression of three Survivin isoforms by quantitative PCR. Survivin was most highly expressed when compared with normal cerebellar tissue. We also investigated Survivin protein expression in 40 paraffin-embedded paediatric medulloblastoma tumours by immunohistochemistry. We found a statistically significant association between the percentage of Survivin-positive cells and histologic subtype, with the large-cell-anaplastic variant expressing Survivin at higher levels than the classic subtype. We also found a statistically significant relationship between the percent of Survivin-positive cells in the tumours and clinical outcome, with higher levels of Survivin correlating with a worse prognosis. In summary, our study demonstrates a role for Survivin as a marker of tumour morphology and clinical outcome in medulloblastoma. Survivin may be a promising future prognostic tool and potential biologic target in this malignancy.
Figures
Figure 1
Transcriptional expression of Survivin, Survivin-2B, and Survivin-deltaEx3 in 19 fresh-frozen medulloblastoma tumours using quantitative PCR. Fold expression compared to normal human cerebellum was calculated using the Relative Standard Curve Method (ABI). ‘A’=Alive, ‘D’=Dead, and ‘U’=Unknown outcome status.
Figure 2
Protein expression in Daoy cells and medulloblastoma tumours. Daoy cell line and two medulloblastoma tumour samples (#18 and #19) stained with the anti-Survivin antibody Novus-500-201 demonstrated three bands at the predicted molecular weights of Survivin, Survivin-2B, and Survivin-deltaEx3.
Figure 3
Kaplan–Meier curve of overall survival (OS) in 40 medulloblastoma patients, from our study population. The solid line represents OS, and the dotted lines represent the 95% confidence intervals.
Figure 4
Protein expression of Survivin in medulloblastoma tumours. Immunohistochemistry of (A) classic (× 140), (B) large-cell-anaplastic (× 270), (C) desmoplastic (× 70), and (D) extremely nodular medulloblastoma (× 70) using NB-500-201 antibody. Red staining indicates Survivin-positive cells. Note the specific nuclear localisation in all of the Survivin-positive cells. The arrow in (C) indicates the high percentage of staining in the internodular areas of a desmoplastic variant.
Figure 5
Box plot graphical representation of percent of cells staining positive with the NB-500-201 antibody in large-cell-anaplastic (LC) tumours vs classic tumours (C) (A), and in tumours of deceased patients vs those in living patients (B). The thick horizontal line within the box represents the mean value. The box itself represents the 25–75% range of data, and the vertical bars extending from the box represent the extreme values.
Similar articles
- Differential expression of survivin splice isoforms in medulloblastomas.
Li XN, Shu Q, Su JM, Adesina AM, Wong KK, Perlaky L, Antalffy BA, Blaney SM, Lau CC. Li XN, et al. Neuropathol Appl Neurobiol. 2007 Feb;33(1):67-76. doi: 10.1111/j.1365-2990.2006.00782.x. Neuropathol Appl Neurobiol. 2007. PMID: 17239009 - Survivin expression in medulloblastoma: a possible marker for survival.
Abdel-Aziz A, Mohamed MA, Akl FM, Taha AN. Abdel-Aziz A, et al. Pathol Oncol Res. 2013 Jul;19(3):413-9. doi: 10.1007/s12253-012-9594-9. Epub 2012 Dec 16. Pathol Oncol Res. 2013. PMID: 23242569 - Survivin is a negative prognostic marker in medulloblastoma.
Pizem J, Cört A, Zadravec-Zaletel L, Popovic M. Pizem J, et al. Neuropathol Appl Neurobiol. 2005 Aug;31(4):422-8. doi: 10.1111/j.1365-2990.2005.00664.x. Neuropathol Appl Neurobiol. 2005. PMID: 16008826 - Role of survivin and its splice variants in tumorigenesis.
Li F. Li F. Br J Cancer. 2005 Jan 31;92(2):212-6. doi: 10.1038/sj.bjc.6602340. Br J Cancer. 2005. PMID: 15611788 Free PMC article. Review. - [Implication of alternative splice transcripts of caspase-3 and survivin in chemoresistance].
Vegran F, Boidot R, Oudin C, Riedinger JM, Lizard-Nacol S. Vegran F, et al. Bull Cancer. 2005 Mar;92(3):219-26. Bull Cancer. 2005. PMID: 15820916 Review. French.
Cited by
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.
Fitzgerald MC, O'Halloran PJ, Connolly NMC, Murphy BM. Fitzgerald MC, et al. Cell Death Dis. 2022 May 14;13(5):460. doi: 10.1038/s41419-022-04900-y. Cell Death Dis. 2022. PMID: 35568716 Free PMC article. Review. - CD44 mediates stem cell mobilization to damaged lung via its novel transcriptional targets, Cortactin and Survivin.
Ouhtit A, Thouta R, Zayed H, Gaur RL, Fernando A, Rahman M, Welsh DA. Ouhtit A, et al. Int J Med Sci. 2020 Jan 1;17(1):103-111. doi: 10.7150/ijms.33125. eCollection 2020. Int J Med Sci. 2020. PMID: 31929744 Free PMC article. - Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor.
Karpinsky G, Krawczyk MA, Izycka-Swieszewska E, Fatyga A, Budka A, Balwierz W, Sobol G, Zalewska-Szewczyk B, Rychlowska-Pruszynska M, Klepacka T, Dembowska-Baginska B, Kazanowska B, Gabrych A, Bien E. Karpinsky G, et al. J Cancer Res Clin Oncol. 2018 Mar;144(3):519-529. doi: 10.1007/s00432-018-2580-1. Epub 2018 Jan 13. J Cancer Res Clin Oncol. 2018. PMID: 29332262 Free PMC article. - Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma.
Fenstermaker RA, Ciesielski MJ, Qiu J, Yang N, Frank CL, Lee KP, Mechtler LR, Belal A, Ahluwalia MS, Hutson AD. Fenstermaker RA, et al. Cancer Immunol Immunother. 2016 Nov;65(11):1339-1352. doi: 10.1007/s00262-016-1890-x. Epub 2016 Aug 30. Cancer Immunol Immunother. 2016. PMID: 27576783 Free PMC article. Clinical Trial. - Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma.
Nair SK, Driscoll T, Boczkowski D, Schmittling R, Reynolds R, Johnson LA, Grant G, Fuchs H, Bigner DD, Sampson JH, Gururangan S, Mitchell DA. Nair SK, et al. J Neurooncol. 2015 Oct;125(1):65-74. doi: 10.1007/s11060-015-1890-2. Epub 2015 Aug 27. J Neurooncol. 2015. PMID: 26311248 Free PMC article.
References
- Altieri D (2003a) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 22: 8581–8589 - PubMed
- Altieri D (2003b) Validating Survivin as a cancer therapeutic target. Nat Rev Cancer 3: 46–54 - PubMed
- Altieri DC, Marchisio C (1999) Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest 79: 1327–1333 - PubMed
- Brown HG, Kepner JL, Perlman EJ, Friedman HS, Strother DR, Duffher PK, Kun LE, Goldthwaite PT, Burger PC (2000) Large cell/anaplastic medulloblastomas: a pediatric Oncology Group Study. J Neuropathol Exp Neurol 59: 857–865 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources