5q21 deletion is often heterogeneous in prostate cancer
Corresponding Author
Martina Kluth
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Correspondence
Martina Kluth, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Email: [email protected]
Search for more papers by this authorZaid Al Kilani
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorCansu Özden
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorKhakan Hussein
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorSohall Frogh
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorChristina Möller-Koop
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorEike Burandt
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorStefan Steurer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorFranziska Büscheck
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorFrank Jacobsen
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorAndreas M. Luebke
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorSarah Minner
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorMaria Christina Tsourlakis
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorDoris Hoeflmayer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorCorinna Wittmer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorThorsten Schlomm
Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorGuido Sauter
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorRonald Simon
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorWaldemar Wilczak
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorCorresponding Author
Martina Kluth
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Correspondence
Martina Kluth, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Email: [email protected]
Search for more papers by this authorZaid Al Kilani
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorCansu Özden
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorKhakan Hussein
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorSohall Frogh
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorChristina Möller-Koop
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorEike Burandt
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorStefan Steurer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorFranziska Büscheck
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorFrank Jacobsen
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorAndreas M. Luebke
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorSarah Minner
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorMaria Christina Tsourlakis
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorDoris Hoeflmayer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorCorinna Wittmer
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorThorsten Schlomm
Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorGuido Sauter
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorRonald Simon
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorWaldemar Wilczak
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorFunding information: Wilhelm Sander-Stiftung, Grant/Award Number: 2015.010.1
Abstract
Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG-negative (28%) than in ERG-positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG-positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.
Supporting Information
| Filename | Description |
|---|---|
| gcc22730-sup-0001-FigureS1a.tifTIFF image, 2.6 MB | Supporting Information Figure 1a. Results of 5q21 and 6q copy number analysis by FISH and ERG expression analysis by immunochemistry in all 10 lissue spots of all 317 arrayed cancers. 6q and ERG data were available from a previous study. Shown are 5q, 6q and ERG normal cases (n=i'1). |
| gcc22730-sup-0002-FigureS1b.tifTIFF image, 2.6 MB | Supporting Inlormation Figure1b. Results of 5q21 and 6q copy number analysis by FISH and ERG expression analysis by immunochemislry in all 10 tissue spots of all 317 arrayed cancers, 6q and ERG data wele avauable from a previous study. Shown are only ERG positivel cases (n=98). |
| gcc22730-sup-0003-FigureS1c.tifTIFF image, 2.6 MB | Supporting Information Figure 1c. Results al 5q21 and 6q copy number analysis by FISH and ERG expression analysis by immunochemistry in all 10 tissue spots of all 317 arrayed cancers. 6q and ERG data were available from a previous study. Shown are A) cases with 5q deletion only (n=9), B) cases with 6q oeleuon only (n=40), and C) 5q deeltian and ERG positivity (n=13). |
| gcc22730-sup-0004-FigureS1d.tifTIFF image, 2.6 MB | Supporting Information Figure 1d. Results of 5q21 and 6q copy number analysis by FISH and ERG expression analysis by immunochemistry in all 10 tissue spots of all 317 arrayed cancers. 6q and ERG data were available from a previous study. Shown are A) cases with 6q deletion and ERG positivity (n=-16), B) cases with 6q and 5q deletion, and C) cases with 5q and Sq deletion as well as ERG posmvity (n=17). |
| gcc22730-sup-0005-FigureS2.tifTIFF image, 756.5 KB | Supporting Information Figure 2. Examples of the distribution of Eq deletion in two tumors. A) Homogenous 5q deleted tumor and B) heterogenous 5q deleted tumor. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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