The Expression of DNA Dependent Protein Kinase Protein in Malignant Lymphoma

ABSTRACT

BACKGROUND: DNA dependent protein kinase (DNA-PK) composed of Ku70, Ku80 and DNA-PK catalytic subunit (DNA-PKcs), plays an important role in the primary repair of break points of damaged DNA and is involved in the recombination of the V, D, and J genes. Loss of DNA-PK may lead to immunodeficiency and malignant lymphomas. This hypothesis has been supported by animal study in a Ku70 knock-out mouse model. The relationship between DNA-PK and human malignant lymphoma has not yet been studied. METHODS: We examined the loss of DNA-PK proteins in 85 representative cases of different subtypes of malignant lymphoma. Immunohistochemical stains for DNA-PK subunits were performed on formalin-fixed and paraffin-embedded tissue sections. RESULTS: Lymphomas demonstrated statistically significant loss of Ku70, Ku80 and DNA-PKcs. T cell lymphomas showed more loss of DNA-PK proteins in comparison with B cell lymphomas. According to the World Health Organization (WHO) classification system, both T cell lymphomas and high-grade subtypes of B cell lymphomas demonstrated similar degree of loss of DNA-PK proteins. CONCLUSIONS: We confirmed the loss of DNA-PK proteins in malignant lymphomas through the results of our study, and the loss of these proteins seems to be more significant in high-grade lymphomas. These findings support the role of DNA-PK as a tumor suppressor gene.