title: Prognostic significance of phospho-histone H3 in prostate carcinoma.
abstract: OBJECTIVE
  Prostate cancer is the second most common cancer in men and the sixth most common cause of death from cancer in men worldwide. Currently, a sufficient pathological distinction between patients requiring further treatment and those for which active surveillance remains an option is still lacking, which leads to the problem of overtreatment. Cell proliferation is routinely assessed by detecting Ki-67 antigen. While Ki-67 is expressed throughout the interphase of proliferating cells, phosphorylation of the chromatin constituent histone H3 occurs only during the late G2 phase and mitosis thus providing a more strict assessment of the mitotic activity. We undertook this study to test whether expression of the recently introduced proliferation marker phospho-histone H3 (pHH3) in prostate carcinoma tissue sections exhibits prognostic significance in comparison with Ki-67.
  
  
  METHODS
  Protein expression of pHH3 and Ki-67 was assessed on TMA consisting of paraffin-embedded tissue from men that had undergone radical prostatectomy. The analysis included triplicate tissue cores of a total of 339 tumor foci. Immunohistochemical staining of pHH3 and Ki-67 was performed and analyzed using Definiens imaging software.
  
  
  RESULTS
  Prostate cancer tissue exhibited a significantly higher frequency of pHH3-positive cells compared to benign prostate tissue. pHH3 expression was significantly correlated with Ki-67 expression. Furthermore, statistical analysis revealed positive correlation between pHH3 expression and PSA levels at diagnosis and in addition negatively correlated with overall survival. In contrast to Ki-67 staining, pHH3 expression did not correlate with Gleason grade.
  
  
  CONCLUSIONS
  Our data point to a conceivable role of pHH3 as prognostic biomarker in prostate carcinoma.
authors.affiliation: Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nowak
authors.forename: Maria A
authors.initials: MA
authors.lastname: Svensson
authors.forename: Jessica
authors.initials: J
authors.lastname: Carlsson
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.forename: Moritz
authors.initials: M
authors.lastname: Kebschull
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Ove
authors.initials: O
authors.lastname: Andrén
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D049109:Cell Proliferation; D005858:Germany / Q000453:epidemiology; D006657:Histones / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods*; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate / Q000639:trends
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D019394:Ki-67 Antigen; D017430:Prostate-Specific Antigen