Defective DNA damage response (DDR) can result in genomic instability (GIN) and 
lead to the transformation into cancer. P53-binding protein 1 (53BP1) belongs to 
a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules 
localize at the sites of DNA double strand breaks (DSBs) and rapidly form 
nuclear foci, the presence of 53BP1 foci can be considered as a cytologic marker 
for endogenous DSBs reflecting GIN. Although it has been proposed that GIN has a 
crucial role in the progression of thyroid neoplasms, the significance of GIN 
during thyroid tumorigenesis remains unclear, particularly in patients. We 
analyzed, therefore, the level of GIN, as detected with immunofluorescence of 
53BP1, in 40 cases of resected thyroid tissues. This study demonstrated a number 
of nuclear 53BP1 foci in thyroid cancers, suggesting a constitutive activation 
of DDR in thyroid cancer cells. Because follicular adenoma also showed a few 
53BP1 nuclear foci, GIN might be induced at a precancerous stage of thyroid 
tumorigenesis. Furthermore, high-grade thyroid cancers prominently exhibited an 
intense and heterogeneous nuclear staining of 53BP1 immunoreactivity, which was 
also observed in radiation-associated cancers and in mouse colonic crypts as a 
delayed response to a high dose ionizing radiation, suggesting increased GIN 
with progression of cancer. Thus, the present study demonstrated a difference in 
the staining pattern of 53BP1 during thyroid carcinogenesis. We propose that 
immunofluorescence analysis of 53BP1 expression can be a useful tool to estimate 
the level of GIN and, simultaneously, the malignant potency of human thyroid 
tumors.