Article: Nuclear expression of Ku70/80 is associated with CHEK2 germline mutations in breast cancer.
Polish journal of pathology : official journal of the Polish Society of Pathologists
2023 Volume 74, Issue 2, Page(s) 75–81
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, ...
| 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. |
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| MeSH term(s) | Female ; Humans ; Breast Neoplasms/genetics ; Checkpoint Kinase 2/genetics ; Germ-Line Mutation ; Image Processing, Computer-Assisted | |||||
| Chemical Substances | Checkpoint Kinase 2 (EC 2.7.1.11) ; CHEK2 protein, human (EC 2.7.11.1) ; XRCC5 protein, human (EC 3.6.4.12) ; Xrcc6 protein, human (EC 3.6.4.12) | |||||
| Language | English | |||||
| Publishing date | 2023-09-20 | |||||
| Publishing country | Poland | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1283064-1 | |||||
| ISSN | 1233-9687 ; 0031-3114 | |||||
| ISSN | 1233-9687 ; 0031-3114 | |||||
| DOI | 10.5114/pjp.2023.129518 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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