title: Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers.
abstract: BACKGROUND
  Altered DNA repair may be associated with aggressive tumour biology and impact upon response to chemotherapy and radiotherapy. We investigated whether expression of human AP endonuclease (APE1), a key multifunctional protein involved in DNA BER, would impact on clinicopathological outcomes in ovarian, gastro-oesophageal, and pancreatico-biliary cancer.
  
  
  METHODS
  Formalin-fixed human ovarian, gastro-oesophageal, and pancreatico-biliary cancers were constructed into TMAs. Expression of APE1 was analysed by IHC and correlated to clinicopathological variables.
  
  
  RESULTS
  In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05). In gastro-oesophageal cancers previously exposed to neoadjuvant chemotherapy, 34.8% (16 out of 46) of tumours were positive in the nucleus and this correlated with shorter overall survival (P=0.005), whereas cytoplasmic localisation correlated with tumour dedifferentiation (P=0.034). In pancreatico-biliary cancer, nuclear staining was seen in 44% (32 out of 72) of tumours. Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068). A trend was noticed with advanced stage (P=0.077).
  
  
  CONCLUSIONS
  Positive clinicopathological correlations of APE1 expression suggest that APE1 is a potential drug target in ovarian, gastro-oesophageal, and pancreatico-biliary cancers.
authors.affiliation: Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, UK.
authors.forename: A
authors.initials: A
authors.lastname: Al-Attar
authors.forename: L
authors.initials: L
authors.lastname: Gossage
authors.forename: K R
authors.initials: KR
authors.lastname: Fareed
authors.forename: M
authors.initials: M
authors.lastname: Shehata
authors.forename: M
authors.initials: M
authors.lastname: Mohammed
authors.forename: A M
authors.initials: AM
authors.lastname: Zaitoun
authors.forename: I
authors.initials: I
authors.lastname: Soomro
authors.forename: D N
authors.initials: DN
authors.lastname: Lobo
authors.forename: R
authors.initials: R
authors.lastname: Abbotts
authors.forename: S
authors.initials: S
authors.lastname: Chan
authors.forename: S
authors.initials: S
authors.lastname: Madhusudan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001661:Biliary Tract Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis
chemical_list: C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase