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Expression and prognostic significance of survivin splice variants in diffusely infiltrating astrocytoma.
- Source :
-
Journal of clinical pathology [J Clin Pathol] 2011 Nov; Vol. 64 (11), pp. 953-9. Date of Electronic Publication: 2011 Jul 05. - Publication Year :
- 2011
-
Abstract
- Background: Alternative splicing of survivin (BIRC5) pre-mRNA generates the common isoform survivin and five additional splice variants: survivin2B, survivinΔEx3, survivin2α, survivin3B and survivin3α. Although the common isoform survivin has been shown to be involved in tumourigenesis and progression of various tumours, including diffusely infiltrating astrocytoma, the expression of other survivin splice variants in astrocytoma has not been fully investigated. Aims To evaluate the expression status and particularly prognostic significance of survivin splice variants in diffusely infiltrating astrocytoma.<br />Methods: mRNA expression of the six survivin variants in 73 diffusely infiltrating astrocytoma and 18 normal brain tissue samples was investigated by using reverse transcription-PCR (RT-PCR), and the total survivin protein expression by western analysis and immunohistochemistry. Association of survivin and its splice variants with tumour grade and prognosis was examined by statistical and survival analysis.<br />Results: The survivin, survivinΔEx3, survivin2B and survivin2α splice variants were significantly elevated in diffusely infiltrating astrocytoma, and were barely detectable or not detectable at all in normal brain tissue. Survivin3B and survivin3α were not detected in these samples. The positive rates of the expressed four variants increased with astrocytoma grade. Significantly, expression of these splice variants was associated with much poorer disease-specific and progression-free survival (Kaplan-Meier analysis, p≤0.002). Cox regression model further indicated survivin2α mRNA expression and nuclear survivin immunostaining to be significant independent negative prognostic factors.<br />Conclusions: The survivin, survivinΔEx3, survivin2B and survivin2α splice variants were significantly elevated in astrocytoma, and were associated with tumour grade and poorer prognosis.
- Subjects :
- Adult
Astrocytoma genetics
Blotting, Western
Brain Neoplasms genetics
Disease Progression
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
Survivin
Alternative Splicing genetics
Astrocytoma metabolism
Brain Neoplasms metabolism
Inhibitor of Apoptosis Proteins metabolism
Neoplasm Proteins metabolism
RNA Precursors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1472-4146
- Volume :
- 64
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of clinical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 21730264
- Full Text :
- https://doi.org/10.1136/jclinpath-2011-200066