| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Human Pathology | ||||
| Verlag: | W B SAUNDERS CO-ELSEVIER INC | ||||
| Ort der Veröffentlichung: | PHILADELPHIA | ||||
| Band: | 37 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 2 | ||||
| Seitenbereich: | S. 143-151 | ||||
| Datum: | 2006 | ||||
| Institutionen: | Medizin > Lehrstuhl für Pathologie Medizin > Lehrstuhl für Urologie | ||||
| Identifikationsnummer: |
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| Stichwörter / 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-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 70175 |
Web of ScienceZusammenfassung
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 ...
Zusammenfassung
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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