[1018] Landscape of Chromosome Number Changes during Prostate Cancer Progression

Julia Stomper, Martin Braun, Wenzel Vogel, Diana Boehm, Veit Scheble, Falko Fend, Sven Perner. University Hospital of Bonn, Bonn, Germany; University Hospital of Tuebingen, Tuebingen, Germany

Background: Genetic instability resulting in both aneuploidy and polyploidy is discussed to be involved in prostate cancer (PCa) development and progression. However, a complete survey of numerical chromosomal changes in PCa is lacking so far. The aim of this study was to comprehensively characterize the ploidy status in PCa with regard to disease progression via fluorescence in situ hybridization (FISH). Since aneuploidy and aggressive disease are often associated with increased tumor cell proliferation, we also assessed the expression of two common mitosis markers within the same PCa cohort.
Design: We studied a cohort comprising 112 localized PCa, 75 PCa with 125 corresponding lymph node metastases, and 42 hormone-refractory distant metastases. Using dual-color FISH, we assessed the cohort for losses and gains of all 24 chromosomes. Conducting immunohistochemistry using the markers pHH3 and Ki67, we quantified the proliferation rate within the same cohort.
Results: We observed a sharp and significant increase in aneuploidy with advancing tumor stage (p<0.01). Whereas 38.1% of localized tumors, 61.3% of lymph node metastasized primary PCa, and 80% of corresponding lymph node metastases displayed an aneuploid karyotype, almost all (97.6%) distant metastases were aneuploid. In general, gains (51.5%) of chromosomes were more common than losses (25.4%). Regarding characteristic copy number changes of single chromosomes, chromosomes X (31.8%), 21 (25.1%), 14 (22.7%), Y (22.2%), 16 (21.9%), 1 (20.6%), and 8 (20.2%) were most frequently altered. Additionally, we found that losses of chromosomes 20 (14.1%), 10 (5%), and 6 (4.9%) accounted for the most frequent monosomies. Noteworthy, an increased degree of cell proliferation was significantly associated with the extent of aneuploidy and higher tumor stage (p<0.01).
Conclusions: Disease progression from localized to hormone-refractory PCa is poorly understood on the molecular level. Here, we accumulate evidence that genomic instability leading to aneuploidy may be a crucial factor in cancerogenesis and the metastatic cascade. Our results further indicate a potential association of increased cell proliferation and numerical chromosomal changes. Together, we provide new insight into the incompletley elucidated chromosomal landscape of PCa. More directly, our study suggests an approach that may help to identify patients at risk of unfavourable clinical course.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 8:30 AM

Platform Session: Section A, Tuesday Morning


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