This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moch, H. Articles by Sauter, G. Search for Related Content PubMed PubMed Citation Articles by Moch, H. Articles by Sauter, G.

Intratumoral Heterogeneity of Von Hippel-Lindau Gene Deletions in Renal Cell Carcinoma Detected by Fluorescence in Situ Hybridization¹

Institute of Pathology [H. M., P. S., L. B., J. R., M. J. M., G. S.] and Clinic for Urology [T. C. G.], University of Basel, CH-4003 Basel, Switzerland

Although chromosome 3p deletions are considered an initial event in clear cell renal cell carcinoma (RCC), the reported prevalence of 3p deletions is highly variable. Because molecular analyses may be influenced by intratumoral heterogeneity, this study was performed to evaluate the genetic heterogeneity of the von Hippel-Lindau (VHL) gene (on 3p25.5) in RCC. Fifty-three clear cell and papillary RCCs were examined by duallabeling fluorescence in situ hybridization with probes for the VHL gene and chromosome 3 centromere. The results were compared with histopathological phenotype, proliferative activity (Ki-67 labeling index) and 8p/17p deletions (both suggested to be linked to RCC progression). A clear-cut VHL deletion (in more than 40% of cells) was detectable in 69% of clear cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic heterogeneity of VHL deletions was seen in clear cell RCCs including VHL-deleted subpopulations with different chromosome 3 counts within individual tumors as well as populations with and without VHL deletions. 8p22 and 17p13 deletions (each of which were detected in 18% of clear cell RCCs) were both linked to VHL deletions. However, 8p and 17p deletions were not associated with tumor grade, stage, or Ki-67 labeling index. The data indicate that some clear cell RCCs may develop independently of VHL alterations.

¹ This study was supported by Swiss National Science Foundation (3200-043969.95), Krebsliga Basel (3/97), Schweizerische Krebsliga (SKL 292-2-1996), and Krebsforschung Schweiz (367-9-1996).

² To whom requests for reprints should be addressed, at Institut für Pathologie der Universität Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland. Phone: 061-2652890; Fax: 061-2653194; E-mail: moch@ubaclu.unibas.ch.

Received 2/24/98. Accepted 4/17/98.

This article has been cited by other articles:

				M. E. Sanders, R. Mick, J. E. Tomaszewski, and F. G. Barr Unique Patterns of Allelic Imbalance Distinguish Type 1 from Type 2 Sporadic Papillary Renal Cell Carcinoma Am. J. Pathol., September 1, 2002; 161(3): 997 - 1005. [Abstract] [Full Text] [PDF]

				J. Torhorst, C. Bucher, J. Kononen, P. Haas, M. Zuber, O. R. Kochli, F. Mross, H. Dieterich, H. Moch, M. Mihatsch, et al. Tissue Microarrays for Rapid Linking of Molecular Changes to Clinical Endpoints Am. J. Pathol., December 1, 2001; 159(6): 2249 - 2256. [Abstract] [Full Text] [PDF]

				F. Jiang, R. Desper, C. H. Papadimitriou, A. A. Schäffer, O.-P. Kallioniemi, J. Richter, P. Schraml, G. Sauter, M. J. Mihatsch, and H. Moch Construction of Evolutionary Tree Models for Renal Cell Carcinoma from Comparative Genomic Hybridization Data Cancer Res., November 1, 2000; 60(22): 6503 - 6509. [Abstract] [Full Text]

				F. Jiang, J. Richter, P. Schraml, L. Bubendorf, T. Gasser, G. Sauter, M. J. Mihatsch, and H. Moch Chromosomal Imbalances in Papillary Renal Cell Carcinoma : Genetic Differences between Histological Subtypes Am. J. Pathol., November 1, 1998; 153(5): 1467 - 1473. [Abstract] [Full Text] [PDF]