title: DNA damage response and its clinicopathological relationship in appendiceal tumors.
abstract: BACKGROUND
  Appendiceal tumors are rare, and their pathogenesis is not well known. DNA damage response (DDR) is a sequence from the detection of damaged DNA to the repair, and its impairment is implicated in the progression of cancers. The aim of the current study is to explore the expression and phosphorylation of checkpoint kinase 2 (Chk2) and TP53, which are key molecules in DDR, and their clinicopathological correlation in the appendiceal tumors.
  
  
  METHODS
  Chk2, phosphorylated Chk2 (pChk2), and TP53 were immunostained in 4 cases of adenoma (AD), 5 non-mucinous adenocarcinomas (AC), 29 low-grade appendiceal mucinous neoplasms (LAMN), and 7 mucinous adenocarcinomas (MAC). Ki-67 labeling index was also evaluated by immunostaining.
  
  
  RESULTS
  Chk2 was highly expressed in the nuclei of all the appendiceal tumors. While pChk2 was high in AD, LAMN, and MAC, it was reduced in AC. Nuclear positive reaction of TP53 was lower in LAMN compared with those of other tumors. The Ki-67 labeling index was slightly lower in LAMN than those in other tumors. The recurrence and death in LAMN is infrequent compared with those in AC and MAC.
  
  
  CONCLUSIONS
  The current study suggested the impairment of DDR in AC and MAC. DDR appeared to be preserved in LAMN, and it may account for low proliferating activity and a favorable clinical course in LAMN.
authors.affiliation: Department of Pathology and Molecular Medicine, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Yajima
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Wada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001063:Appendiceal Neoplasms / Q000235:genetics* / Q000473:pathology*; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D064447:Checkpoint Kinase 2