title: Ataxia-telangiectasia-mutated protein kinase levels stratify patients with pancreatic adenocarcinoma into prognostic subgroups with loss being a strong indicator of poor survival.
abstract: OBJECTIVE
  Recently, aberrations in the gene encoding for ataxia-telangiectasia-mutated (ATM) protein kinase have been reported for pancreatic ductal adenocarcinomas (PDAC). These findings argue that ATM deficiency may play a role during carcinogenesis. Therefore, in this study, we investigated the clinical relevance of ATM expression and ATM activation in PDAC.
  
  
  METHODS
  Both ATM expression and nuclear phosphoSer1981-ATM levels were assessed by immunohistochemistry in a cohort of 133 PDAC and correlated with clinicopathological parameters.
  
  
  RESULTS
  We found stratification in prognostic subgroups. Complete loss of Ser1981-ATM was indicative of the worst prognosis (median survival, 10.8 vs 14.3 months [low expression] vs 31.1 months [high expression], P < 0.001). Similarly, analysis of ATM expression demonstrated absent expression levels of ATM to be associated with dismal prognosis (median survival, 9.6 months), whereas expression of ATM in general was associated with increased survival (17.7 months, P = 0.001).
  
  
  CONCLUSIONS
  Our analysis shows that both ATM expression and activated ATM are prognostic markers in PDAC with respect to standard clinicopathological parameters. These results suggest that ATM should be further explored as prognostic as well as predictive factor with respect to conventional chemotherapies and for putative synthetic lethal approaches.
authors.affiliation: From the *Department of General, Visceral and Transplantation Surgery, and †Institute of Pathology, Charité University Hospital, Berlin; ‡Institute of Pathology, University Hospital Heidelberg; and §National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kamphues
authors.forename: Roberta
authors.initials: R
authors.lastname: Bova
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.forename: Frederick
authors.initials: F
authors.lastname: Klauschen
authors.forename: Alexander
authors.initials: A
authors.lastname: Muckenhuber
authors.forename: Bruno V
authors.initials: BV
authors.lastname: Sinn
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Benjamin
authors.initials: B
authors.lastname: Goeppert
authors.forename: Volker
authors.initials: V
authors.lastname: Endris
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins