Flow Cytometric Bromodeoxyuridine/Deoxyribonucleic Acid Bivariate Analysis for Predicting Tumor Invasiveness of Upper Tract Urothelial Cancer

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Abstract
We previously reported that flow cytometric bromodeoxyuridine/deoxyribonucleic acid (DNA) bivariate analysis can provide important information on the malignant potential of bladder cancer. Therefore, in the current study we further evaluated upper tract urothelial tumors to clarify whether DNA/bromodeoxyuridine bivariate analysis can provide additional prognostic information on patients with upper tract urothelial tumor. A total of 43 upper tract urothelial tumors that were resected by nephroureterectomy was analyzed. Flow cytometric DNA ploidy and bromodeoxyuridine labeling were determined by an in vitro bromodeoxyuridine labeling method. DNA diploid tumors were associated with an 85.9% 3-year survival rate compared to 36.5% for DNA aneuploid tumors. On the other hand, 11 high bromodeoxyuridine labeled tumors demonstrated a 16.4% 3-year survival rate compared to 82.4% for those with low bromodeoxyuridine labeled tumors. Multivariate survival analysis using the Cox proportional regression model was performed to identify the most informative factors for prognosis, with the single most important factor being histological tumor stage. Nearly as important and the next factor to be chosen was tumor grade, followed by bromodeoxyuridine labeling index status. DNA ploidy status did not influence clinical outcome. Thereafter, when actuarial 3-year survival rates according to the bromodeoxyuridine labeling index status in grade 3 tumors were estimated, 68.4% and 16.7% 3-year survival rates were observed in cases of low and high bromodeoxyuridine labeling index tumors, respectively. These results indicate that flow cytometric bromodeoxyuridine/DNA bivariate analysis may be useful in dividing patients with grade 3 upper tract urothelial carcinoma into 2 different prognosis groups.