Portal de Periódicos da CAPES

MULTIFOCAL TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND UPPER URINARY TRACT: MOLECULAR SCREENING OF CLONAL ORIGIN BY CHARACTERIZING CD44 ALTERNATIVE SPLICING PATTERNS

2004; Lippincott Williams & Wilkins; Volume: 172; Issue: 3 Linguagem: Inglês

10.1097/01.ju.0000129541.23460.48

1527-3792

Hideaki Miyake, Isao Hara, Sadao Kamidono, Hiroshi Eto,

Tissue Engineering and Regenerative Medicine

No AccessJournal of UrologyInvestigative Urology1 Sep 2004MULTIFOCAL TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND UPPER URINARY TRACT: MOLECULAR SCREENING OF CLONAL ORIGIN BY CHARACTERIZING CD44 ALTERNATIVE SPLICING PATTERNS HIDEAKI MIYAKE, ISAO HARA, SADAO KAMIDONO, and HIROSHI ETO HIDEAKI MIYAKEHIDEAKI MIYAKE , ISAO HARAISAO HARA , SADAO KAMIDONOSADAO KAMIDONO , and HIROSHI ETOHIROSHI ETO View All Author Informationhttps://doi.org/10.1097/01.ju.0000129541.23460.48AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism during cancer initiation. We assessed whether multifocal transitional cell carcinoma of the urothelium is due to field change and/or intraluminal seeding and implantation. Materials and Methods: In a series of 24 patients with synchronous and/or metachronous multiple urothelial cancers we performed reverse transcription-polymerase chain reaction analysis using a set of primers capable of amplifying all CD44 splice variant isoforms. After polymerase chain reaction products were electrophoresed band intensities with areas corresponding to the major isoforms (that is CD44s, CD44v10 and CD44v8–10) were quantified, and CD44v10-to-CD44s and CD44v8–10-to-CD44s ratios were calculated. Moreover, p53 gene mutations in exons 4 to 11 were screened by direct DNA sequencing. Results: Of these 24 cases 18 showed similar CD44v10-to-CD44s and CD44v8–10-to-CD44s ratios in among multiple urothelial cancers in each case. However, in the remaining 6 cases these ratios were quite different among multiple cancer lesions. Furthermore, different types of p53 mutation were detected among multiple cancer lesions in only 2 of 24 cases, which also indicated different patterns of CD44 alternative splicing. Conclusions: These findings suggest that at least some multiple transitional cell carcinomas of the urothelium seem to be of independent origin based on the analysis of alternative RNA splicing of CD44. Moreover, this hypothesis was further supported by the evaluation of p53 gene mutation. References 1 : Pathways of development and progression in bladder cancer: new correlations between clinical observations and molecular mechanisms. Semin Urol1993; 11: 177. Google Scholar 2 : Molecular screening of multifocal transitional cell carcinoma of the bladder using p53 mutations as biomarkers. Clin Cancer Res1996; 2: 1795. Google Scholar 3 : Bladder cancer—field versus clonal origin. N. Engl J Med1992; 326: 759. Google Scholar 4 : Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma and associated vesicoureteral reflux. J Urol1985; 133: 468. Link, Google Scholar 5 : Molecular genetic alterations in superficial and locally advanced human bladder cancer. Cancer Res1991; 51: 5405. Medline, Google Scholar 6 : Clonal and chronological genetic analysis of multifocal cancer of the bladder and upper urinary tract. Cancer Res1998; 58: 5835. Google Scholar 7 : Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet1993; 342: 1087. Crossref, Medline, Google Scholar 8 : Interaction between CD44 and hyarulonate is directory implicated in the regulation of tumor development. J Exp Med1994; 180: 53. Google Scholar 9 : Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase. Mol Carcinog1993; 7: 212. Google Scholar 10 : Expression of CD44R1 adhesion molecule in colon carcinomas and metastases. Lancet1993; 341: 725. Google Scholar 11 : Expression of CD44 adhesion molecule in non-papillary renal cell carcinomas and normal kidneys. Urology1999; 54: 562. Google Scholar 12 : Highly specific and sensitive detection of malignancy in urine samples from patients with urothelial cancer by CD44v8–10/CD44v10 competitive RT-PCR. Int J Cancer1998; 79: 560. Google Scholar 13 : Expression patterns of CD44 adhesion molecule in testicular germ cell tumors and normal testes. Am J Pathol1998; 152: 1157. Google Scholar 14 : Over expression of CD44v8–10 in urinary exfoliated cells as an independent prognostic predictor in patients with urothelial cancer. J Urol2002; 167: 1282. Link, Google Scholar 15 : Altered expression of CD44 in human prostate cancer during progression. Am J Clin Pathol1996; 106: 647. Google Scholar 16 : Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem1987; 162: 156. Crossref, Medline, Google Scholar 17 : p53 function and dysfunction. Cell1992; 70: 523. Google Scholar 18 : Multiple head and neck tumors: evidence for a common clonal origin. Cancer Res1996; 56: 2484. Medline, Google Scholar 19 : Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternative spliced exons. Proc Natl Acad Sci USA1992; 89: 12160. Google Scholar 20 : Interaction between CD44 and hyaluronic acid regulates human prostate cancer development. J Urol1998; 160: 1562. Link, Google Scholar From the Departments of Urology, Hyogo Medical Center for Adults, Akashi and Kobe University School of Medicine, Kobe, Japan© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 172Issue 3September 2004Page: 1127-1129 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsgenes, p53cell adhesion moleculesurotheliumcarcinoma, transitional cellMetricsAuthor Information HIDEAKI MIYAKE More articles by this author ISAO HARA More articles by this author SADAO KAMIDONO More articles by this author HIROSHI ETO More articles by this author Expand All Advertisement PDF downloadLoading ...