Development of the practical methods to predict radiosensitivity of tumors with immunohistchemistry

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Purpose : DNA-dependent protein kinase (DNA-PK), a serine/theronine 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) which are the major lethal lesions induced by ionizing radiation. We investigated the expression of DNA-PK subunits in human tumors.Materials and Methods : We examined immunohistochemically the biopsy specimens of 46 patients with oropharyngeal carcinoma and 24 patients with hypopharyngeal carcinoma who had been treated with radiotherapy.Results : Immunopositivity to Ku70, Ku85, and DNA-PKcs was found in all patients. The staining of Ku70, 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 Ku70 or DNA-PKcs was seen in 69 of 70 tumors and that of Ku 85 was seen in all 70 patients. The radiation responses of the primary tumors which stained weakly with Ku70 or DNA-PKcs were excellent.Conclusion : Low expression of DNA-PK could be related to the decline of its catalytic activity and of capability to repair radiation-induced DSB. These results suggest that defects in DNA-PK activity might contribute to clinical radiosensitivity.