Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations.
- Author:
Xinyi ZHU
1
;
Tian TIAN
;
Miao RUAN
;
Jia RAO
;
Wentao YANG
;
Xu CAI
;
Menghong SUN
;
Guangqi QIN
;
Zhonghua ZHAO
;
Jiong WU
;
Zhimin SHAO
;
Ruohong SHUI
;
Zhen HU
Author Information
- Publication Type:Original Article
- Keywords: BRCA1 genes; BRCA2 genes; Breast neoplasms; DNA repair; Poly (ADP-ribose) polymerase-1
- MeSH: Asian Continental Ancestry Group*; Breast Neoplasms*; Breast*; Checkpoint Kinase 2; Cytoplasm; DNA Damage*; DNA Repair; DNA*; Estrogens; Genes, BRCA1; Genes, BRCA2; Humans; Immunohistochemistry; Phosphotransferases; Rad51 Recombinase; Receptor, Epidermal Growth Factor
- From:Journal of Breast Cancer 2018;21(3):297-305
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.
