Hafner, Christian and Knuechel, Ruth and Zanardo, Livia and Dietmaier, Wolfgang and Blaszyk, Hagen and Cheville, John and Hofstaedter, Ferdinand and Hartmann, Arndt (2001) Evidence for oligoclonality and tumor spread by intraluminal seeding in multifocal urothelial carcinomas of the upper and lower urinary tract. ONCOGENE, 20 (35). pp. 4910-4915. ISSN 0950-9232
Full text not available from this repository. (Request a copy)Abstract
Multifocality and recurrence of urothelial carcinoma may result from either the field effect of carcinogens leading to oligoclonal tumors or monoclonal tumor spread. Previous molecular studies, favoring the monoclonality hypothesis, are mostly limited to the urinary bladder. We investigated genetic alterations in a total of 94 synchronous or metachronous multifocal tumors from 19 patients with at least one tumor both in the upper and lower urinary tract. Loss of heterozygosity (LOH) was determined using eight markers on chromosome 9 and one marker on 17p13 (p53). Microsatellite instability was investigated at six loci and protein expression of MSH2 and MLH1 was evaluated by immunohistochemistry. In addition, exons 5-9 of the p53 gene were sequenced. Deletions at chromosome 9 were found in 73% of tumors and at 17p13 in 18% of tumors. There was no significant difference in the frequency of LOH in the upper and lower urinary tract. Deletions at 9p21 were significantly correlated with invasive tumor growth. The pattern of deletion revealed monoclonality of all tumors in nine patients. In five patients there were at least two tumor clones with different genetic alterations. In four of these patients the different clones occured in the bladder and subsequently in the ureter and renal pelvis. All four patients with p53 mutations revealed identical mutations in all tumors. Thus, multifocal urothelial carcinomas are frequently monoclonal, whereas others show oligoclonality, providing molecular evidence for field cancerization. Intraluminal tumor cell seeding appears to be an important mechanism of multifocal occurence and recurrence of urothelial carcinomas.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSITIONAL-CELL CARCINOMA; BLADDER-CANCER; MICROSATELLITE INSTABILITY; FIELD CANCERIZATION; CLONAL ORIGIN; P53 MUTATION; LOW-GRADE; DELETION; urothelial carcinoma; upper and lower urinary tract; LOH; oligoclonality; p53 mutation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2021 06:30 |
| Last Modified: | 14 Dec 2021 06:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/41195 |
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