ORIGINAL ARTICLE
Nuclear expression of Ku70/80 is associated with CHEK2 germline mutations in breast cancer
1
Department of Pathology, Pomeranian Medical University, Szczecin, Poland
2
Department of Medical Biology, Medical University of Warsaw, Warsaw, Poland
3
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
Submission date: 2023-06-05
Acceptance date: 2023-06-17
Publication date: 2023-07-17
Corresponding author
Paweł Domagała
Paweł Domagała, MD, PhD Department of Pathology Pomeranian Medical University 1 Unii Lubelskiej St. 71-252 Szczecin, Poland
Paweł Domagała, MD, PhD Department of Pathology Pomeranian Medical University 1 Unii Lubelskiej St. 71-252 Szczecin, Poland
Pol J Pathol 2023;74(2):75-81
KEYWORDS
TOPICS
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.
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.
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