PMID- 23512229
OWN - NLM
STAT- MEDLINE
DCOM- 20140930
LR  - 20220516
IS  - 1433-8726 (Electronic)
IS  - 0724-4983 (Linking)
VI  - 31
IP  - 6
DP  - 2013 Dec
TI  - Landscape of chromosome number changes in prostate cancer progression.
PG  - 1489-95
LID - 10.1007/s00345-013-1051-1 [doi]
AB  - 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.
FAU - Braun, Martin
AU  - Braun M
AD  - Institute of Pathology, Department of Prostate Cancer Research, University 
      Hospital of Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
FAU - Stomper, Julia
AU  - Stomper J
FAU - Kirsten, Robert
AU  - Kirsten R
FAU - Adler, David
AU  - Adler D
FAU - Vogel, Wenzel
AU  - Vogel W
FAU - Bohm, Diana
AU  - Bohm D
FAU - Wernert, Nicolas
AU  - Wernert N
FAU - Kristiansen, Glen
AU  - Kristiansen G
FAU - Perner, Sven
AU  - Perner S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130320
PL  - Germany
TA  - World J Urol
JT  - World journal of urology
JID - 8307716
RN  - 0 (Biomarkers)
RN  - 0 (Histones)
SB  - IM
MH  - Aged
MH  - *Aneuploidy
MH  - Biomarkers/metabolism
MH  - *Cell Proliferation
MH  - Cohort Studies
MH  - *Disease Progression
MH  - Histones/metabolism
MH  - Humans
MH  - Lymphatic Metastasis/diagnosis/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis/diagnosis/genetics/pathology
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Prostatic Neoplasms/diagnosis/*genetics/*pathology
EDAT- 2013/03/21 06:00
MHDA- 2014/10/01 06:00
CRDT- 2013/03/21 06:00
PHST- 2013/01/10 00:00 [received]
PHST- 2013/03/01 00:00 [accepted]
PHST- 2013/03/21 06:00 [entrez]
PHST- 2013/03/21 06:00 [pubmed]
PHST- 2014/10/01 06:00 [medline]
AID - 10.1007/s00345-013-1051-1 [doi]
PST - ppublish
SO  - World J Urol. 2013 Dec;31(6):1489-95. doi: 10.1007/s00345-013-1051-1. Epub 2013 
      Mar 20.