title: DNA damage response-related proteins in gastric cancer: ATM, Chk2 and p53 expression and their prognostic value.
abstract: OBJECTIVE
  The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma.
  
  
  METHODS
  Two independent cohorts, a training set (n=524) and validation set (n=394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions were examined by immunohistochemistry using tissue microarray.
  
  
  RESULTS
  ATM loss, Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively. In the training set, the aberrant expressions of ATM, Chk2, or p53 were significantly associated with an advanced TNM stage and poor disease-specific survival. This association was verified in the validation set. Chk2 positivity and p53 negativity were significantly related to a prolonged disease-specific survival. Also, patients with nonaberrant expressional levels of all 3 DDR-related proteins had a more favorable outcome than others. Multivariate analyses showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as independent prognostic factors of poor disease-specific survival.
  
  
  CONCLUSIONS
  This study elucidated the prognostic implications of DDR-related proteins, and suggests that their aberrant expressions play critical roles in the development and progression of gastric cancer.
authors: Department of Pathology, Seoul National University Hospital, Seoul, South Korea.
authors: Hee Eun
authors: HE
authors: Lee
authors: Nayoung
authors: N
authors: Han
authors: Min A
authors: MA
authors: Kim
authors: Hye Seung
authors: HS
authors: Lee
authors: Han-Kwang
authors: HK
authors: Yang
authors: Byung Lan
authors: BL
authors: Lee
authors: Woo Ho
authors: WH
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D064447:Checkpoint Kinase 2 / Q000032:analysis / Q000096:biosynthesis*; D004249:DNA Damage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human