title: Dysregulation of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in advanced retinoblastoma.
abstract: BACKGROUND
  Retinoblastoma (RB) is a childhood eye tumour. Dysregulation of DNA repair may not only influence pathogenesis but could also adversely impact on response to cytotoxic chemotherapy frequently used in RB therapy. We studied the expression of human apurinic/apyrimidinic endonuclease (APE1), a key multifunctional protein involved in DNA base excision repair in RB.
  
  
  METHODS
  Expression of APE1 was evaluated by immunohistochemistry in a series of 55 RBs and in retina. In tumours, APE1 expression was analysed in cytoplasm and nucleus independently and correlated with histopathological features, including invasion, differentiation and International Intraocular Retinoblastoma Classification groups. Relative APE1 mRNA and protein expressions were evaluated by real-time PCR and western blot. The expression of APE1 in tumour groups was compared with retinal tissue.
  
  
  RESULTS
  APE1 cytoplasmic expression was observed in 98% and nuclear positivity was observed in 83% of tumours analysed. Tumour cells invading the optic nerve showed predominant cytoplasmic immunoreactivity. An inverse correlation between cytoplasmic and nuclear positivity was observed. Real-time PCR revealed an increase in APE1 transcripts compared with retina. Western blot revealed a decreased protein concentration compared with retinal tissue.
  
  
  CONCLUSIONS
  This is the first study of APE1 expression in RB. Our observation suggests that subcellular localisation of APE1 is altered in RB. APE1 could be a potential drug target in RB.
authors.affiliation: Larsen and Toubro Ocular Pathology Department, Vision Research Foundation, Sankara Nethralaya, , Chennai, India.
authors.forename: Job
authors.initials: J
authors.lastname: Sudhakar
authors.forename: Vikas
authors.initials: V
authors.lastname: Khetan
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Madhusudan
authors.forename: Subramanian
authors.initials: S
authors.lastname: Krishnakumar
mesh_terms: D015153:Blotting, Western; D002467:Cell Nucleus / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000201:enzymology; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000201:enzymology* / Q000235:genetics; D012175:Retinoblastoma / Q000201:enzymology* / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Child health (paediatrics); Pathology