Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations

Xinyi Zhu; Tian Tian; Miao Ruan; Jia Rao; Wentao Yang; Xu Cai; Menghong Sun; Guangqi Qin; Zhonghua Zhao; Jiong Wu; Zhimin Shao; Ruohong Shui; Zhen Hu

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저자정보: Xinyi Zhu (Fudan University Shanghai Cancer Center) Tian Tian (Fudan University Shanghai Cancer Center) Miao Ruan (Fudan University Shanghai Cancer Center) Jia Rao (Fudan University Shanghai Cancer Center) Wentao Yang (Fudan University Shanghai Cancer Center) Xu Cai (Fudan University Shanghai Cancer Center) Menghong Sun (Fudan University Shanghai Cancer Center) Guangqi Qin (Fudan University Shanghai Cancer Center) Zhonghua Zhao (Shanghai Medical College Fudan University) Jiong Wu (Fudan University Shanghai Cancer Center) Zhimin Shao (Fudan University Shanghai Cancer Center) Ruohong Shui (Fudan University Shanghai Cancer Center) Zhen Hu (Department of Breast Surgery Fudan University Shanghai Cancer Center China)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.21 No.3

발행연도: 2018.1

수록면: 297 - 305 (9page)

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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.

참고문헌 (30)

참고문헌 신청

King MC / 2003 / Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2 / Science 302:643~646

Shih HA / 2002 / BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic / J Clin Oncol 20:994~999

Yang X / 2015 / Identification of a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population by next-generation sequencing / PLoS One 10:e0125571

Aleskandarany M / 2015 / DNA damage response markers are differentially expressed in BRCA-mutated breast cancers / Breast Cancer Res Treat 150:81~90

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