title: Landscape of chromosome number changes in prostate cancer progression.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute of Pathology, Department of Prostate Cancer Research, University Hospital of Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Julia
authors.initials: J
authors.lastname: Stomper
authors.forename: Robert
authors.initials: R
authors.lastname: Kirsten
authors.forename: David
authors.initials: D
authors.lastname: Adler
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.forename: Diana
authors.initials: D
authors.lastname: Böhm
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000368:Aged; D000782:Aneuploidy; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D006657:Histones / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D006657:Histones