Do the survivin (BIRC5) splice variants modulate or add to the prognostic value of total survivin in breast cancer?

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Publication year
2006Source
Clinical Chemistry, 52, 9, (2006), pp. 1693-1700ISSN
Publication type
Article / Letter to editor

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Organization
Chemical Endocrinology
Medical Oncology
Clinical Chemistry
Journal title
Clinical Chemistry
Volume
vol. 52
Issue
iss. 9
Page start
p. 1693
Page end
p. 1700
Subject
IGMD 6: Hormonal regulation; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 3: Translational research; ONCOL 5: Aetiology, screening and detection; UMCN 1.1: Functional Imaging; UMCN 5.1: Genetic defects of metabolism; UMCN 5.2: Endocrinology and reproductionAbstract
BACKGROUND: A total of 4 additional splice variants (survivin-DeltaEx3, survivin 2alpha, survivin-2B, and survivin-3B) have been described for survivin [baculoviral IAP repeat-containing protein (BIRC-5), approved gene symbol BIRC5], which has been implicated in both inhibition of apoptosis and regulation in mitosis in many tumor types. In this study, we assessed whether the survivin splice variants modulate or add to the prognostic value of total survivin in breast cancer. METHODS: With quantitative reverse transcription-PCR, we measured mRNA concentrations of survivin and all variants in tumor tissue from 275 patients with breast cancer and associated these with clinicopathologic characteristics and relapse-free survival. RESULTS: Total survivin, survivin-DeltaEx3, and survivin 2alpha mRNA levels were associated with young age and ductal histology. Total survivin and survivin-DeltaEx3 were highest in samples with advanced histological grade, whereas patients with 4-9 involved lymph nodes expressed less survivin-2B mRNA than those with 1-3 involved nodes. All variants were higher in tumors negative for steroid hormone receptors. Total survivin, survivin 2alpha, and survivin-3B were associated with poor relapse-free survival in univariate analyses. Survivin 2alpha and survivin-3B added to the prognostic value of total survivin in multivariate analyses. In addition, the prognostic value of total survivin was evident only in the presence of higher expression levels of these 2 variants. CONCLUSIONS: All variants of survivin exhibited particular associations with clinicopathologic characteristics (age, histology, grade, and steroid hormone receptor status) of breast cancer patients. Survival analyses suggest a modulating role of survivin 2alpha and survivin-3B on the biological function of total survivin.
This item appears in the following Collection(s)
- Academic publications [204980]
- Electronic publications [103240]
- Faculty of Medical Sciences [81051]
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