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Uridine 5'diphospho‐glucuronosyltransferase 1A expression as an independent prognosticator in urothelial carcinoma of the upper urinary tract
Author(s) -
Izumi Koji,
Inoue Satoshi,
Ide Hiroki,
Fujita Kazutoshi,
Mizushima Taichi,
Jiang Guiyang,
Yamaguchi Seiji,
Fushimi Hiroaki,
omura Norio,
Miyamoto Hiroshi
Publication year - 2018
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.13528
Subject(s) - uridine , medicine , glucuronosyltransferase , urinary system , carcinoma , cancer research , pathology , enzyme , chemistry , rna , biochemistry , gene , microsome
Objective To determine the expression status of uridine 5'diphospho‐glucuronosyltransferase 1A, a major phase II drug metabolism enzyme, in upper urinary tract urothelial carcinoma, as well as to assess its prognostic significance. Methods We immunohistochemically stained for uridine 5'diphospho‐glucuronosyltransferase 1A in tissue microarray consisting of 99 upper urinary tract urothelial carcinoma samples and paired non‐neoplastic urothelial tissues. We also assessed the effect of uridine 5'diphospho‐glucuronosyltransferase 1A knockdown on urothelial cancer cell growth. Results Uridine 5'diphospho‐glucuronosyltransferase 1A was positive in 92.9% (27.3% weak [1+], 37.4% moderate [2+], 28.3% strong [3+]) of tumors, which was significantly ( P < 0.001) lower than in benign urothelial tissues (98.8%; 3.5% 1+, 18.8% 2+, 76.4% 3+). All 37 (100%) non‐muscle‐invasive versus 55 (88.7%) of 62 muscle‐invasive tumors ( P = 0.043) were immunoreactive for uridine 5'diphospho‐glucuronosyltransferase 1A. The rates of moderate‐to‐strong uridine 5'diphospho‐glucuronosyltransferase 1A expression and its positivity were also strongly associated with the absence of concomitant carcinoma in situ ( P = 0.034) and lymphovascular invasion ( P = 0.016), respectively. However, there were no statistically significant associations between uridine 5'diphospho‐glucuronosyltransferase 1A expression and tumor grade or pN/M status. Uridine 5'diphospho‐glucuronosyltransferase 1A loss in M0 tumors was strongly associated with lower progression‐free survival ( P < 0.001) and cancer‐specific survival ( P < 0.001) rates. Multivariate analysis further identified a strong correlation of uridine 5'diphospho‐glucuronosyltransferase 1A positivity with reduced cancer‐specific mortality (hazard ratio 0.28, P = 0.018). Meanwhile, uridine 5'diphospho‐glucuronosyltransferase 1A knockdown in urothelial cancer cells resulted in significant increases in their viability and migration. Conclusions These results suggest a preventive role of uridine 5'diphospho‐glucuronosyltransferase 1A signals in the development and progression of upper urinary tract urothelial carcinoma. Loss of uridine 5'diphospho‐glucuronosyltransferase 1A expression might serve as an independent predictor of poor prognosis in patients with upper urinary tract urothelial carcinoma.