1997 Fiscal Year Final Research Report Summary
Molecular biological analysis of urothelial cancers using short-term cultures of urinary exfoliated cells
| Project/Area Number |
08671813
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
OKUNO Hiroshi Kyoto University, Urology, Instructor, 医学研究科, 助手 (90263079)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUTANI Yoichi Kyoto University, Urology, Instructor, 医学研究科, 助手 (10243031)
KAKEHI Yoshiyuki Kyoto University, Urology, Assistant professor, 医学研究科, 講師 (20214273)
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| Project Period (FY) |
1996 – 1997
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| Keywords | urothelial / urinary exfoliated cell / short-term culture / intraluminal tumor recurrcncc / p53 / immunocytochemistry |
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| Research Abstract |
Urothelial cancers, in particular of upper urinary tract cancers, is multifocal synchronous and/or metachronous tumor development in the heterotopic urothelium. We investigated the abilities of exfoliated cells in the urine of patients with urothelial cancers to colonize and proliferate in vitro. Short-term cultures of 129 urine samples obtained from patients with urothelial cancers and 53 samples from healthy volunteers were compared as to the growth potential of urinary-exfoliated cells and clinico-pathological features, in particular tumor localization and evidence of intraluminal tumor recurrence. Primary cell outgrowth occurred in 112 (86.8%) of the 129 cell cultures from the patients and in 29 (54.7%) of the 53 from the healthy volunteers (p<0.0001). "Sufficient cell growth" (more than 10^5 cells per flask) was obtained for 77 (59.7%) of the 129 cultures from patients and 7(13.2%) of the 53 from the healthy volunteers (p<0.0001). In terms of tumor localization, the rate of suffic
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ient cell growth was significantly higher for patients with upper urinary tract tumor (21/25,84.0%) than for those with bladder tumor (56/104,53.8%) (p=0.0062). Proportional hazard regression analysis showed that only the growth potential of the urinary-exfoliated cells was significantly predictive of intravesical tumor recurrence in patients with superficial bladder tumors (p=0.011). The potentials for the colonization and proliferation of urinary-exfoliated cells are associated with intraluminal multifocal tumorrecurrence of urothelial cancers.
Mutation of the p53 gene together with allelic loss of chromosome 17p correlates well with high grade and invasiveness of urothelial cancer. Using the short-term culture system, immunocytochemical detection of p53 was conducted. Results of immunochemical analyzes of the p53 in the urine cells and those in the tumor samples were identical in 92.1% of the patients. Culture of exfoliated cells in urine is a good method for the molecular diagnosis of urothelial cancer. In particular, it is a non-invasive examination that should prove useful for the early detection and intensive follow-up of tumorswith p53 mutation. Less
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