title: Loss of histone variant macroH2A2 expression associates with progression of anal neoplasm.
abstract: OBJECTIVE
  The macroH2A histone variants are epigenetic marks for inactivated chromatin. In this study, we examined the expression of macroH2A2 in anal neoplasm from anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (SCC).
  
  
  METHODS
  AIN and anal SCC samples were analysed for macroH2A2 expression, HIV and human papilloma virus (HPV). The association of macroH2A2 expression with clinical grade, disease recurrence, overall survival and viral involvement was determined.
  
  
  RESULTS
  macroH2A2 was expressed in normal squamous tissue and lower grade AIN (I and II). Expression was lost in 38% of high-grade AIN (III) and 71% of anal SCC (p=0.002). Patients with AIN with macroH2A2-negative lesions showed earlier recurrence than those with macroH2A2-positive neoplasm (p=0.017). With anal SCC, macroH2A2 loss was more prevalent in the HPV-negative tumours.
  
  
  CONCLUSIONS
  Loss of histone variant macroH2A2 expression is associated with the progression of anal neoplasm and can be used as a prognostic biomarker for high-grade AIN and SCC.
authors.affiliation: Department of Surgery, University of California San Diego Health System, San Diego, California, USA Rebecca and John Moores Cancer Center, University of California San Diego Health System, San Diego, California, USA Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Wan-Hsiang
authors.initials: WH
authors.lastname: Hu
authors.affiliation: Department of Pathology, School of Medicine, University of California, San Diego, California, USA.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyai
authors.affiliation: Department of General Surgery, Baystate Medical Center, Springfield, Massachusetts, USA.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Sporn
authors.affiliation: Department of Surgery, University of California San Diego Health System, San Diego, California, USA Rebecca and John Moores Cancer Center, University of California San Diego Health System, San Diego, California, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Luo
authors.affiliation: Rebecca and John Moores Cancer Center, University of California San Diego Health System, San Diego, California, USA Division of Hematology-Oncology, Department of Medicine, School of Medicine, University of California, San Diego, California, USA.
authors.forename: Jean Y J
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of California San Diego Health System, San Diego, California, USA Department of Surgery, Veteran's Administration Medical Center, University of California, San Diego Healthcare System, San Diego, California, USA.
authors.forename: Bard
authors.initials: B
authors.lastname: Cosman
authors.affiliation: Department of Surgery, University of California San Diego Health System, San Diego, California, USA Rebecca and John Moores Cancer Center, University of California San Diego Health System, San Diego, California, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramamoorthy
mesh_terms: D000328:Adult; D001005:Anus Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D006657:Histones; C120756:macroH2A histone
keywords: ANUS; CANCER; HIV; HPV