Back to Search
Start Over
BUBR1 overexpression predicts disease-specific survival after nephroureterectomy in patients with upper tract urothelial carcinoma.
- Source :
-
Japanese journal of clinical oncology [Jpn J Clin Oncol] 2016 Aug; Vol. 46 (8), pp. 754-61. Date of Electronic Publication: 2016 May 12. - Publication Year :
- 2016
-
Abstract
- Objective: To date, there are few reliable markers to distinguish tumors with aggressive characteristics in upper tract urothelial carcinoma. The purpose of this study was to identify a biomarker related to genetic instability (chromosomal instability or microsatellite instability) with prognostic value, in patients with upper tract urothelial carcinoma.<br />Methods: Expression of chromosomal instability-related markers (BUBR1, p53, polo-like kinase 1) and microsatellite instability-related markers (mismatch repair proteins, MLH1 and MSH2) were assessed by immunohistochemistry in 100 patients who had radical nephroureterectomy for upper tract urothelial carcinoma. Numerical aberrations of chromosomes 7, 9 and 17 were evaluated by fluorescence in situ hybridization, which allowed an estimation of the degree of chromosomal instability. BUB1B copy number was examined by array-based comparative genomic hybridization in 32 patients with upper tract urothelial carcinoma.<br />Results: BUBR1 status was most significantly correlated with chromosomal instability-related and low mismatch repair parameters, according to the molecular biomarkers examined. Overexpression of BUBR1 is frequently detected in tumors with higher histological grade (P < 0.0001) and is significantly associated with chromosomal instability (P = 0.0071). Array-based comparative genomic hybridization revealed that no tumors (0%) showed BUB1B amplification and gain, indicating that overexpression of BUBR1 was independent of BUB1B copy number. For disease-specific survival, BUBR1 overexpression, lymphovascular invasion, pathological tumor stage, pathological lymph node involvement and low MSH2 expression were significant prognostic factors in univariate analyses. In multivariate analyses, BUBR1 overexpression was an independent prognostic factor for disease-specific survival (P = 0.0483, risk ratio 3.76, 95% confidence interval: 1.01-18.43).<br />Conclusions: BUBR1 may have significant potential as a biomarker for estimating disease-specific survival in patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.<br /> (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Aged
Aged, 80 and over
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Carcinoma, Transitional Cell genetics
Carcinoma, Transitional Cell mortality
Carcinoma, Transitional Cell pathology
Chromosomal Instability
Comparative Genomic Hybridization
Disease-Free Survival
Female
Gene Dosage
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Kaplan-Meier Estimate
Lymphatic Metastasis
Male
Middle Aged
Multivariate Analysis
MutS Homolog 2 Protein genetics
MutS Homolog 2 Protein metabolism
Nephrectomy
Prognosis
Protein Serine-Threonine Kinases genetics
Retrospective Studies
Up-Regulation
Ureteral Neoplasms genetics
Ureteral Neoplasms mortality
Ureteral Neoplasms pathology
Carcinoma, Transitional Cell surgery
Protein Serine-Threonine Kinases metabolism
Ureteral Neoplasms surgery
Subjects
Details
- Language :
- English
- ISSN :
- 1465-3621
- Volume :
- 46
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Japanese journal of clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 27174960
- Full Text :
- https://doi.org/10.1093/jjco/hyw060