eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
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without publication fees
2/2023
vol. 74
 
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abstract:
Original paper

Nuclear expression of Ku70/80 is associated with CHEK2 germline mutations in breast cancer

Rosik Jakub
1
,
Machaj Filip
1, 2
,
Bodnar Daniel
1
,
Hybiak Jolanta
1
,
Huzarski Tomasz
3
,
Cybulski Cezary
3
,
Lubiński Jan
3
,
Domagała Wenancjusz
1
,
Paweł Domagała
1

  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
POL J PATHOL 2023; 74 (2): 75-81
DOI: https://doi.org/10.5114/pjp.2023.129518
Online publish date: 2023/07/17
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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.
keywords:

breast cancer, CHEK2, Ku70/80
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