| Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Laboratory Investigation | ||||
| Verlag: | NATURE PUBLISHING GROUP | ||||
| Ort der Veröffentlichung: | NEW YORK | ||||
| Band: | 82 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 11 | ||||
| Seitenbereich: | S. 1553-1561 | ||||
| Datum: | 2002 | ||||
| Institutionen: | Medizin > Lehrstuhl für Pathologie Biologie und Vorklinische Medizin > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / Keywords: | URINARY-BLADDER NEOPLASIA; UROTHELIAL CARCINOMA; HUMAN CANCER; CHROMOSOME-9; PROGRESSION; MUTATIONS; REGIONS; ORIGIN; CARCINOGENESIS; OLIGOCLONALITY; | ||||
| Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 72666 |
Web of ScienceZusammenfassung
Common and clinically important features of urothelial carcinomas are multifocality and a high rate of recurrence. Molecular studies demonstrated that multifocal tumors are frequently composed of one tumor clone spreading throughout the urothelial tract. A combination of histologic and genetic mapping of cystectomy specimens from bladder cancer patients is a valuable tool to study bladder ...
Zusammenfassung
Common and clinically important features of urothelial carcinomas are multifocality and a high rate of recurrence. Molecular studies demonstrated that multifocal tumors are frequently composed of one tumor clone spreading throughout the urothelial tract. A combination of histologic and genetic mapping of cystectomy specimens from bladder cancer patients is a valuable tool to study bladder carcinogenesis and tumor cell spread by correlating urothelial morphologic features and defined genetic alterations. In the present study, the primary tumors of 14 cystectomy specimens were investigated for p53 protein overexpression by immunohistochemistry and p53 gene mutation by genomic sequencing. Seven tumors showed a strong nuclear staining for the p53 protein. In six of seven tumors, a p53 gene mutation was detected. Allele-specific PCR of defined p53 mutations was established in five of six cases with a p53 mutation. Subsequent screening of the entire urothelial lining of each cystectomy specimen by allele-specific PCR revealed p53-mutant cell clones in urothelial patches with carcinoma in situ and dysplasia, but also frequently in histomorphologically normal urothelium adjacent to the tumor. The pattern of tumor cell spread indicated a continuous intraurothelial growth of the p53-mutant clone. P53 immunohistochemistry visually confirmed the presence of mutant cells in most of these samples. We conclude that allele-specific PCR is a highly sensitive and reliable method for tracking specific p53 mutant clones in the urothelium. Moreover, the detection of p53-mutant cells in histologically normal or preneoplastic urothelial areas in four patients with invasive bladder cancer indicates an extensive intraurothelial tumor cell spread. The excellent correlation of immunohistochemically positive urothelial patches with the presence of a specific mutation highlights the biologic significance of p53-positive cells in the urothelium of tumor patients.
Metadaten zuletzt geändert: 19 Dez 2024 15:37
Altmetric