title: Early DNA damage response in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  The aim of this study was to clarify the association between the DNA damage response mediated by p53-binding protein 1 (53BP1) in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma.
  
  
  METHODS
  A retrospective analysis was conducted of 11 patients with positive ductal margins with carcinoma in situ. To evaluate the early DNA damage response, the nuclear staining pattern of 53BP1 was examined by immunofluorescence. TUNEL analysis was used to calculate the apoptotic index.
  
  
  RESULTS
  Of the 11 tumor specimens of carcinoma in situ, seven showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and four showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the seven tumor specimens with 53BP1 inactivation compared to the four with 53BP1 activation (median apoptotic index, 1 vs. 22 %; p = 0.003). The cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (cumulative 5-year local recurrence rate, 60 vs. 0 %; p = 0.019).
  
  
  CONCLUSIONS
  Clinically evident local recurrence of residual carcinoma in situ at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan. wakait@med.niigata-u.ac.jp
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shirai
authors.forename: Jun
authors.initials: J
authors.lastname: Sakata
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Korita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D017734:Bile Ducts, Extrahepatic; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D004249:DNA Damage; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D016577:Pancreaticoduodenectomy; D018709:Statistics, Nonparametric; D015996:Survival Rate; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1