Landscape of chromosome number changes in prostate cancer progression.

ABSTRACT

PURPOSE: Both genetic instability resulting in aneuploidy and increased proliferative activity are common features of tumor development and progression. Cytometric evaluation of tumor ploidy status was recently suggested as a prognostic marker. However, in prostate cancer (PCa), a chromosome-specific evaluation is lacking. With the present study, we sought to identify distinct chromosomal changes to complement cytometric results concerning the diagnosis and prognosis of PCa patients. METHODS: We assessed a cohort of 428 PCa specimens (186 localized PCa, 75 lymph node metastasized PCa, 125 lymph node metastases, 42 hormone-refractory distant metastases) for numerical alterations of all 24 chromosomes by using fluorescence in situ hybridization (FISH). Conducting immunohistochemistry with phosphorylated histone H3 (PHH3) and Ki-67, we quantified the proliferation rate. FISH results were fit in a linear model and tested for predictive power. RESULTS: As expected, we observed a significant increase in aneuploidy with advancing tumor stage. Similarly, an increased expression of the mitotic marker PHH3 was significantly associated with aneuploidy and higher pT-stage. We found aneusomy of chromosomes 4, 6, 20, and X to be indicative of lymph node metastasized PCa. However, with an AUC of 65%, this set of chromosomal changes was poorly suited to distinguish non-metastasized and lymph node metastasized primary tumors. CONCLUSION: Our results provide thorough insight into the so far incompletely elucidated chromosomal landscape of PCa. While overall ploidy status and PHH3 expression in primary tumors indicate advanced disease, a FISH-based test for distinct alterations does not seem to be beneficial for diagnostic or prognostic decisions.