Expression of Ku86 confers favorable outcome of tonsillar carcinoma treated with radiotherapy.
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.
Friesland
Signe
S
Department of Oncology and Pathology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Kanter-Lewensohn
Lena
L
Tell
Roger
R
Munck-Wikland
Eva
E
Lewensohn
Rolf
R
Nilsson
Anders
A
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
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