title: HP1γ expression is elevated in prostate cancer and is superior to Gleason score as a predictor of biochemical recurrence after radical prostatectomy.
abstract: BACKGROUND
  Aberrant chromatin structure in cancer cells results from altered proteins involved in its packaging. Heterochromatin protein 1 gamma (HP1γ) is a non-histone heterochromatic protein that functions to maintain chromatin stability and is important in embryonic development. Given an interest in the role developmental genes play in cancer, we investigated HP1γ expression in prostate cancer (PCa) and its prognostic associations.
  
  
  METHODS
  Tissue microarrays consisting of benign (N = 96), localized cancer (N = 146), metastatic PCa (N = 44), and HGPIN (N = 50) were immunoflourescently stained for HP1γ and Ki-67. Using a novel, automated quantitative imaging system, VECTRA™, epithelial staining in both the nucleus and cytoplasm was quantified and compared against clinicopathologic variables.
  
  
  RESULTS
  HP1γ is significantly elevated in HGPIN (80%), localized PCa (76%), and metastatic PCa (98%) compared to benign tissues from both the nuclear and cytoplasmic compartments (P < 0.0001). Increased nuclear and total HP1γ expression was associated with Gleason score (P = 0.02 and P = 0.04 respectively). Given known binding to the C-terminus of Ki-67, a co-expression analysis was performed that revealed a correlation between nuclear and cytoplasmic HP1γ and Ki-67 (Pearson Coefficient 0.321 and 0.562 respectively, P < 0.0001). Cox survival analysis demonstrated that cytoplasmic HP1γ expression was an independent prognostic marker and out-performed pathological Gleason score for predicting PSA-recurrence after radical prostatectomy.
  
  
  CONCLUSIONS
  In this first detailed analysis of HP1γ expression in cancer, VECTRA™ demonstrates compartmentalized and total HP1γ protein expression is increased in PCa and that expression correlates with clinical outcomes better than Gleason score. Given the critical role HP1γ plays in chromatin organization and gene expression, it represents a novel prognostic and therapeutic target.
authors.affiliation: School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53750, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Slezak
authors.forename: Matthew
authors.initials: M
authors.lastname: Truong
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: David
authors.initials: D
authors.lastname: Jarrard
mesh_terms: D000328:Adult; D000368:Aged; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011467:Prostate / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
chemical_list: C518294:CBX3 protein, human; D002868:Chromosomal Proteins, Non-Histone; D019394:Ki-67 Antigen