title: Expression of Ku86 confers favorable outcome of tonsillar carcinoma treated with radiotherapy.
abstract: BACKGROUND
  To determine possible molecular markers for predicting radiosensitivity in squamous cell carcinoma, we have examined the relationship between pretreatment expression of the DNA damage recognition complex DNA-PK, its in vitro substrates, p53 and MDM2, local tumor control after radiotherapy (RT), and patient survival.
  
  
  METHODS
  Formalin-fixed tumor biopsy specimens from 79 previously untreated patients with tonsillar carcinoma were analyzed by immunohistochemical methods.
  
  
  RESULTS
  Tumors expressing high levels of Ku86 had better locoregional control in contrast to tumors expressing low levels of Ku86 (p =.023). Survival of patients with tumors expressing high levels of DNA-PKcs was significantly better than survival of patients with tumors expressing low levels of DNA-PKcs (p =.0024). p53 and MDM2 status alone did not correlate with survival of patients. However, patients with p53 tumors and high DNA-PKcs expression had significantly better survival than patients with p53+ tumors expressing low levels of DNA-PKcs (p =.0018). Furthermore, survival of patients with high expression of DNA-PKcs or Ku86 and low MDM2 levels was significantly better when compared with survival of patients with low DNA-PKcs or Ku86 and high MDM2 (p =.0017 and p =.0034, respectively).
  
  
  CONCLUSIONS
  High expression of DNA-PKcs/Ku86 in combination with p53 negativity in tonsillar carcinoma correlates with better survival of patients. Identifying tumors with a phenotype predicting poor survival may be used to optimize treatment of patients with radioresistant tumors.
authors.affiliation: Department of Oncology and Pathology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Friesland
authors.forename: Lena
authors.initials: L
authors.lastname: Kanter-Lewensohn
authors.forename: Roger
authors.initials: R
authors.lastname: Tell
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.forename: Anders
authors.initials: A
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear / Q000032:analysis* / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000032:analysis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D004265:DNA Helicases; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D015996:Survival Rate; D014067:Tonsillar Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
chemical_list: D034961:Antigens, Nuclear; D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; C463462:KU70 protein, Arabidopsis; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen