@Article{Jakub2023,
journal="Polish Journal of Pathology",
issn="1233-9687",
volume="74",
number="2",
year="2023",
title="Nuclear expression of Ku70/80 is associated with CHEK2 germline mutations in breast cancer",
abstract="Ku70/80 protein inhibitors reduce the repair of DNA double-strand breaks via the Ku70/80 pathway, so they can be used to treat cancers with Ku70/80 overexpression. Since the association of Ku70/80 with germline CHEK2 mutations in breast cancer is unknown, in this study we evaluated the expression of Ku70/80 in breast cancers with germline CHEK2 mutations.  Immunohistochemistry with a Ku70/80 antibody on tissue microarrays from  225 CHEK2-associated breast cancers was used and automatically assessed with computerized image analysis.  We report that the vast majority of breast cancers expressed high level of nuclear Ku70/80 and a small percentage of tumors (3.5%) were negative for Ku70/80 expression. There was a significant difference between the nuclear Ku70/80 expression in CHEK2-associated vs. CHEK2-non-associated breast cancers in all tumors (p = 0.009), and in the estrogen receptor (ER) positive subgroup of breast cancers (p = 0.03).  This study is the first reporting an association of Ku70/80 expression with CHEK2 germline mutations in breast cancer. The results suggest that evaluation of Ku70/80 expression in breast cancer may improve the selection of breast cancer patients for Ku70/80 inhibitor therapy, and point to CHEK2-associated breast cancer and a subset of ER-positive breast cancer as potential suitable targets for such therapy.",
author="Jakub, Rosik
and Filip, Machaj
and Daniel, Bodnar
and Jolanta, Hybiak
and Tomasz, Huzarski
and Cezary, Cybulski
and Jan, Lubiński
and Wenancjusz, Domagała
and Domagała, Paweł",
pages="75--81",
doi="10.5114/pjp.2023.129518",
url="http://dx.doi.org/10.5114/pjp.2023.129518"
}