1. BUBR1 overexpression predicts disease-specific survival after nephroureterectomy in patients with upper tract urothelial carcinoma
- Author
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Kazuhiro Nagao, Hiroaki Matsumoto, Nakanori Fuji, Shigeru Sakano, Ryo Inoue, Yoshiaki Yamamoto, Hideyasu Matsuyama, Atsunori Oga, Hiroshi Hirata, Keita Kobayashi, Yoshihisa Kawai, Jumpei Akao, and Taku Misumi
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Lymphovascular invasion ,Gene Dosage ,Kaplan-Meier Estimate ,Protein Serine-Threonine Kinases ,MLH1 ,Nephrectomy ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Chromosomal Instability ,Chromosome instability ,Biomarkers, Tumor ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In Situ Hybridization, Fluorescence ,Aged ,Retrospective Studies ,Aged, 80 and over ,Carcinoma, Transitional Cell ,Comparative Genomic Hybridization ,medicine.diagnostic_test ,Ureteral Neoplasms ,business.industry ,Microsatellite instability ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Up-Regulation ,MutS Homolog 2 Protein ,030104 developmental biology ,Oncology ,MSH2 ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Cancer research ,Biomarker (medicine) ,Female ,business ,Fluorescence in situ hybridization ,Comparative genomic hybridization - 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. 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. 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
- Published
- 2016