Correlation between recurrent chromosomal deletions status obtained on tissue cores and local invasive and systemic prostate cancer growth.

Abstract

24 Background: A variety of chromosomal deletions are known to occur frequently in prostate cancer, but the clinical significance of most of these deletions is unknown. To learn more about epidemiology, associations with other molecular features, and relevance for key clinical endpoints, several recurrent deletions were analyzed on a large-scale tissue microarray platform. Methods: A tissue microarray containing 11,156 prostate cancers was analyzed by fluorescence in situ hybridization (FISH) with dual-labeling probes including PTEN (10q23), TP53 (17p13.1), CHD1 (5q21), and MAP3K7 (6q15) together with their respective centromere probes. Patients were stratified into three major biological groups (organ confined, locally advanced, and systemic tumor growth) according to their multidimensional long-term follow up data. In addition, ERG fusion status and tumor cell proliferation (Ki67 labeling index) of all cancers were determined by immunohistochemistry. Results: Deletions were seen for PTEN in 17.9% of 6,122, TP53 in 14.7% of 7,604, CHD1 in 9.9% of 7,026, and for MAP3K7 in 18.7% of 3,528 interpretable cases. All deletions were strongly linked to a positive (PTEN, TP53) or negative ERG status (CHD1, MAP3K7, p<0.0001 each) and early prostate-specific antigen recurrence. The combination of deletion information provided even better prognostic information, showing a dose dependent relationship between the number of deletions and the growth pattern (organ confined, local invasive, or systemic) of the tumor. Patients with no deletion had a 16.8% risk for local invasive and only 8.9% risk for systemic tumor growth, whereas the respective figures were 17.9% and 44.6% in patients with more than or equal to three deletions (p<0.001). The chance of having an organ confined tumor was 68.0% for patients with no deletion and 23.1% for patients with more than or equal to three deletions (p<0.001), respectively. Conclusions: Our data show, that these analyzed chromosomal deletions are tightly linked with ERG status in prostate cancer and that the deletion status obtained on small tissue cores correlates with key biological tumor features. Combinatorial analysis of genomic alterations in prostate biopsies might provide clinically relevant information.