Abstract 5196: Prognostic relevance of the most common chromosomal deletions in prostate cancer.
Authors: Kluth Martina , Burkhardt Lia , Krohn Antje , Gjoni Jovisa , Haß Thomas , Galal Rami , Schlomm Thorsten , Simon Ronald , Sauter Guido , Minner Sarah Jane Pauline 
Published: August 2014

A variety of chromosomal deletions are known to occur frequently in prostate cancer. Target genes and clinical significance of most of these deletions are unknown. To learn more about epidemiology, association with tumor phenotype, relevance for PSA recurrence and associations with other molecular features, several relevant deletions were analyzed on a large-scale tissue microarray platform in this project.

For the purpose of this study, a tissue microarray containing 11,156 prostate cancers was analyzed by fluorescence in situ hybridization (FISH). All cancers were analyzed with dual-labeling probes including PTEN (10q23), TP53 (17p13.1), FOXP1 (3p14.1), CHD1 (5q21) and MAP3K7 (6q15) together with their respective centromere probes. In addition, ERG fusion status and tumor cell proliferation (Ki67 labeling index) of all cancers were determined by immunohistochemistry. Deletions were seen for PTEN in 17.9% of 6,122, TP53 in 14.7% of 7,604, FOXP1 in 9.2% of 6,059, CHD1 in 9.9% of 7,026, and for MAP3K7 in 18.7% of 3,528 interpretable cases. All deletions were strongly linked to the ERG status (p&lt;0.0001 each). In ERG positive/negative cancers, the deletion frequency was 27%/11% for PTEN, 22%/9% for TP53, 22%/7% for FOXP1, 6%/18% for CHD1, and 11%/28% for MAP3K7. The frequency of all these deletions increased significantly with tumor stage and grade. This was most prominently true for TP53, PTEN and MAP3K7 (p&lt;0.0001 each). In addition, there was a significant association of most deletions with the likelihood of PSA recurrence (PTEN, TP53, MAP3K7, CHD1: p&lt;0.0001; FOXP1: p=0.1486).

The combination of deletion information provided even better prognostic information. There was a dose dependent relationship between the number of deletions and PSA recurrence. Tumors with no deletion had the best clinical outcome followed by cancers, with one, two, and three or more deletions (p&lt;0.0001). Particular strong prognostic information was obtained by combining PTEN and p53 deletions. Patients with none of these alterations had 17% PSA recurrence while the respective figure was 40% on patients with both deletions.

In summary, these data show, that chromosomal deletions are tightly linked with ERG status in prostate cancer and that most of these deletions have clinical relevance. Combinatorial analysis of genomic alterations in prostate cancer might provide clinically relevant information.

Citation Format: Martina Kluth, Lia Burkhardt, Antje Krohn, Jovisa Gjoni, Thomas Haß, Rami Galal, Thorsten Schlomm, Ronald Simon, Guido Sauter, Sarah Jane Pauline Minner. Prognostic relevance of the most common chromosomal deletions in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5196. doi:10.1158/1538-7445.AM2013-5196