Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients

被引：19
|
作者：
Park, See-Hyoung [1 ]
Noh, Sang Jae [2 ,3 ]
Kim, Kyoung Min [2 ,3 ]
Bae, Jun Sang [2 ,3 ]
Kwon, Keun Sang [3 ,4 ]
Jung, Sung Hoo [3 ,5 ]
Kim, Jung Ryul [3 ,6 ]
Lee, Ho [3 ,7 ]
Chung, Myoung Ja [2 ,3 ]
Moon, Woo Sung [2 ,3 ]
Kang, Myoung Jae [2 ,3 ]
Jang, Kyu Yun [2 ,3 ]
机构：
[1] Stanford Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Sch Med, Stanford, CA 94305 USA
[2] Chonbuk Natl Univ, Sch Med, Dept Pathol, Res Inst Clin Med,Chonbuk Natl Univ Hosp,Biomed R, Jeonju 561180, South Korea
[3] Res Inst Endocrine Sci, Jeonju, South Korea
[4] Chonbuk Natl Univ, Sch Med, Dept Prevent Med, Res Inst Clin Med,Chonbuk Natl Univ Hosp,Biomed R, Jeonju 561180, South Korea
[5] Chonbuk Natl Univ, Sch Med, Dept Surg, Res Inst Clin Med,Chonbuk Natl Univ Hosp,Biomed R, Jeonju 561180, South Korea
[6] Chonbuk Natl Univ, Sch Med, Dept Orthopaed Surg, Res Inst Clin Med,Chonbuk Natl Univ Hosp,Biomed R, Jeonju 561180, South Korea
[7] Chonbuk Natl Univ, Sch Med, Dept Forens Med, Res Inst Clin Med,Chonbuk Natl Univ Hosp,Biomed R, Jeonju 561180, South Korea
来源：
TRANSLATIONAL ONCOLOGY | 2015年 / 8卷 / 04期
基金：
新加坡国家研究基金会;
关键词：
OVARIAN-CARCINOMA; GROWTH-FACTOR; CANCER; PROGNOSIS; REPAIR; ASSOCIATION; MUTATIONS;
D O I：
10.1016/j.tranon.2015.04.004
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), gamma H2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, gamma H2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, gamma H2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS), and relapse-free survival (RFS) by univariate analysis. Multivariate analysis revealed the expression of PARP1, gamma H2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and gamma H2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001). The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, gamma H2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.
引用
收藏
页码：239 / 249
页数：11
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