| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Human Pathology | ||||
| Publisher: | W B SAUNDERS CO-ELSEVIER INC | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 37 | ||||
| Number of Issue or Book Chapter: | 2 | ||||
| Page Range: | pp. 143-151 | ||||
| Date: | 2006 | ||||
| Institutions: | Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Urologie | ||||
| Identification Number: |
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| Keywords: | HUMAN URINARY-BLADDER; UROTHELIAL CARCINOMAS; GENETIC ALTERATIONS; CANCER; CHROMOSOME-9; OLIGOCLONALITY; MUTATIONS; DELETIONS; SPREAD; DNA; multifocal bladder cancer; fluorescence in situ hybridization; LOH analysis; clonality; organ mapping | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 70175 |
Web of ScienceAbstract
The clonality status Of multifocal bladder tumors is still controversially discussed with experimental evidence for both monoclonality and field cancerization. Methodologically, loss of heterozygosity (LOH) and genomic sequencing analyses are widely Used in clonality analysis of malignant tumors. In the present study, We Used LOH analysis and genomic sequencing in combination With fluorescence ...
Abstract
The clonality status Of multifocal bladder tumors is still controversially discussed with experimental evidence for both monoclonality and field cancerization. Methodologically, loss of heterozygosity (LOH) and genomic sequencing analyses are widely Used in clonality analysis of malignant tumors. In the present study, We Used LOH analysis and genomic sequencing in combination With fluorescence ill situ hybridization (FISH) and extensive histopathologic whole-organ mapping to determine the clonal relationship Of multifocal bladder cancer disease. Tissue Sections (I cm(2)) covering the entire urothelial lining were systematically dissected from 2 cystectomy specimens (cystectomy 1, no urothelial lesions, bladder infiltration by a leiomyosarcoma of the vaginal wall; cystectomy 2, multifocal pT3G3 tumors). The location of each sample was documented (bladder mapping). Urothelial cells were microdissected for LOH (chromosomes 9, 17p) and FISH analysis (CDKI2 (9p21), FACC (9q22), p53 (17p13.1), and centromeric probes for corresponding chromosome). Exons 5 to 9 of the p53 gene were sequenced ill all tumor samples. No chromosomal alterations were detected in the cystectomy specimen without urothelial malignancies. The tumor-bearing bladder showed all increasing frequency of deletions with increasing malignancy of the investigated lesions. LOH analysis detected deletions only oil chromosomes 9p and 17p. In contrast, FISH analysis revealed deletions of all investigated genes at chromosomes 9p, 9q, and 17p in all samples analyzed (preneoplastic and neoplastic tissue). An identical p53 mutation in codon 281 was found in all 7 analyzable tumor samples. Combination of molecular data with histopathologic bladder mapping suggested a monoclonal development of the multifocal lesions mostly via intraurothelial migration. Our data strengthen the results from recently published studies that patients with advanced urothelial carcinoma seem to have a monoclonal panurothelial disease in most cases. FISH showed a much higher sensitivity for detection of chromosomal losses than classical LOH analysis.. especially in preneoplastic and small lesions. Combining 3 molecular approaches together with histopathologic organ mapping presents a valuable tool to determine the clonality status of multifocal bladder tumors. (c) 2006 Elsevier Inc. All rights reserved.
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