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首页> 外文期刊>Journal of Breast Cancer >Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations
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Expression of DNA Damage Response Proteins and Associations with Clinicopathologic Characteristics in Chinese Familial Breast Cancer Patients with BRCA1/2 Mutations

机译：DNA损伤反应蛋白的表达及与中国临床乳腺癌特征的BRCA1 / 2突变的关联。

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Purpose pThe 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 pWe 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 pIn 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 pThe 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.
机译：目的>尚未分析中国患者中具有BRCA1，BRCA2或非BRCA1 / 2突变的家族性乳腺癌中DNA损伤应答蛋白的特征性表达。我们的研究旨在评估微头蛋白1（BRIT1），ATM丝氨酸/苏氨酸激酶（ATM），检查点激酶2（CHEK2），BRCA1，RAD51重组酶（RAD51）和聚（ADP-核糖）聚合酶1（PARP）的差异表达-1）并建立具有不同突变状态的中国家族性乳腺癌的概况。方法>我们从183例家族性乳腺癌患者中构建了5个组织芯片（其中BRCA1突变31例; BRCA2突变14例;非BRCA1 / 2突变138例）。用于免疫组织化学分析的DNA反应和修复标记包括BRIT1，ATM，CHEK2，BRCA1，RAD51和PARP-1。在BRCA1 / 2突变的肿瘤中分析了这些蛋白的表达。还分析了病理特征与BRCA1 / 2突变状态之间的关系。结果>在家族性乳腺癌患者中，BRCA1突变的肿瘤更为常见，核级高，雌激素受体/孕激素受体/人表皮生长因子受体2阴性，Ki-67低和CK5 / 6阳性。与BRCA2和非BRCA1 / 2突变肿瘤相比，BRCA1突变肿瘤具有更低的CHEK2和更高的细胞质BRIT1表达。与其他组相比，与BRCA2相关的肿瘤显示出更高的CHEK2和细胞质RAD51表达。 BRCA1 / 2相关肿瘤中的核PARP-1表达显着高于非BRCA1 / 2突变肿瘤。此外，我们在BRCA1 / 2突变组中发现了相当多的PARP-1阴性表达病例。结论>与BRCA1相关的中国家族性乳腺癌的临床病理发现与其他研究结果相似。具有BRCA1 / 2突变的中国家族性乳腺癌患者可能具有不同DNA损伤反应蛋白的独特表达。在中国BRCA1 / 2突变的乳腺癌患者中PARP-1表达的降低可能会影响PARP-1抑制剂的治疗效果。

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