The significance of 53BP1 nuclear foci as a universal tumor tissue marker

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The presence of sporadic DNA double strand breaks (DSBs) is considered as a characteristic feature of genomic instability (GIN). It has been proposed that GIN has a crucial role during several carcinogenesis, and is associated with malignant potential of neoplasms. The presence of 53BP1 nuclear foci (NF) can be a cytologic marker for endogenous DSBs reflecting GIN. This study analyzed the level of GIN, as detected with immunofluorescence of 53BP1 expression, in a variety of resected tumors to evaluate the significance of 53BP1 expression as a universal tumor tissue marker. In results : 1) a number of 53BP1NF and abnormal type of 53BP1 expression were demonstrated in thyroid cancers, suggesting a high level of GIN ; 2) during skin carcinogenesis, GIN seems to be induced at the precancerous stage with constitutive activation of DNA damage response (DDR). Furthermore, invasive cancers exhibited abnormal 53BP1 staining, reflecting a disruption of DDR; 3) The number of 53BP1NF in uterine cervical cells appeared to increase with progression during carcinogenesis and to be significantly associated with the expression of human papilloma virus (HPV) signals.