Clinical studies of immunohistochemical staining of DNA-dependent protein kinase in oropharyngeal and hypopharyngeal carcinomas.
OBJECTIVE
DNA-dependent protein kinase (DNA-PK), a serine/threonine kinase composed of p470 catalytic subunit (DNA-PKcs) and p85/p70 heterodimer (Ku antigen), is considered a critical enzyme in the repair of the DNA double-strand breaks (DSB) that are the major lethal lesions induced by ionizing radiation. We investigated the expression of DNA-PK subunits in human tumors.


METHODS
We examined immunohistochemically the biopsy specimens of 44 patients with oropharyngeal carcinoma and 32 patients with hypopharyngeal carcinoma who had been treated with radiotherapy.


RESULTS
Immunopositivity to Ku85 and DNA-PKcs was found in all patients. The staining of Ku85 and DNA-PKcs was nuclear, with none of the normal epithelial cells or malignant cells exhibiting cytoplasmic or membrane immunoreactivity. Normal epithelial cells were all stained intensely. In tumors, intense nuclear staining of DNA-PKcs was seen in 75 of 76 tumors, while that of Ku85 was seen in all 76 patients. The radiation responses of a primary tumor that was stained weakly with DNA-PKcs were excellent.


CONCLUSIONS
Our results suggest the possibility of predicting the intrinsic radiosensitivity of human tumors in clinics able to perform immunohistochemical analysis of DNA-PK.
Sakata
K
K
Department of Radiology, Sapporo Medical University School of Medicine, Japan.
Matsumoto
Y
Y
Satoh
M
M
Oouchi
A
A
Nagakura
H
H
Koito
K
K
Hosoi
Y
Y
Hareyama
M
M
Suzuki
N
N
D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D007150:Immunohistochemistry; D008297:Male; D009687:Nuclear Proteins; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases