Landscape of chromosome number changes in prostate cancer progression

• Published in: World journal of urology Vol. 31; no. 6; pp. 1489 - 1495
• Main Authors: Braun, Martin, Stomper, Julia, Kirsten, Robert, Adler, David, Vogel, Wenzel, Böhm, Diana, Wernert, Nicolas, Kristiansen, Glen, Perner, Sven
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2013; Springer Nature B.V
• Subjects: Aged; Aneuploidy; Biomarkers - metabolism; Cell Proliferation; Chromosome number; Chromosomes; Cohort Studies; Disease Progression; Fluorescence in situ hybridization; Genomic instability; Histone H3; Histones; Histones - metabolism; Humans; Hybridization; Immunohistochemistry; Lymph nodes; Lymphatic Metastasis - diagnosis; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Lymphatic system; Male; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis - diagnosis; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Nephrology; Oncology; Original Article; Ploidy; Predictive Value of Tests; Prognosis; Prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Tumors; Urology; Aneuploidy; Chromosome number change; Prostate cancer; Proliferative activity
• ISSN: 0724-4983; 1433-8726
• DOI: 10.1007/s00345-013-1051-1

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.