title: Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma.
abstract: BACKGROUND
  High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone-associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC.
  
  
  METHODS
  Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki-67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t-test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival.
  
  
  RESULTS
  H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035; HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT.
  
  
  CONCLUSIONS
  Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Henderson
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.forename: Penvadee
authors.initials: P
authors.lastname: Pattanaprichakul
authors.forename: Patricia
authors.initials: P
authors.lastname: Fox
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Torres-Cabala
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.forename: Hunter W
authors.initials: HW
authors.lastname: Richards
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Curry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000401:mortality / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones
keywords: H3K79me3T80ph; Merkel cell carcinoma; PHH3; biomarker; histones