Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Hum Pathol. 2019 Feb;84:231-238. doi: 10.1016/j.humpath.2018.10.004. Epub 2018 Oct 16.
Some sporadic triple-negative breast cancers (TNBCs) share similar clinicopathological and molecular characteristics to BRCA1/2-mutant breast cancers, a phenotype described as "BRCAness." Identifying BRCAness in TNBCs could expand the target group for platinum salts and poly(adenosine diphosphate-ribose) polymerase inhibitors. The aims of our study were to assess the clinical validity of BRCA1/2 promoter methylation and BRCA1-like genomic profile to identify BRCAness and to evaluate its correlations with clinicopathological features in TNBCs. Formalin-fixed, paraffin-embedded tissues and fresh tissues of 151 primary invasive TNBCs were collected. BRCA1/2 promoter methylation and BRCA1-like genomic profile were detected using methylation-specific multiplex ligation-dependent probe amplification and multiplex ligation-dependent probe amplification assay, respectively. BRCA1/2 messenger RNA expression was evaluated by quantitative reverse-transcription polymerase chain reaction. Of the 151 patients, 38 (25.2%) showed BRCA1 promoter methylation. Of the 124, 52 (41.9%) had a BRCA1-like multiplex ligation-dependent probe amplification profile. The frequency of BRCAness phenotype was 54.8% (68/124). BRCA1 germline mutation and BRCA1 promoter methylation were mutually exclusive (P = .002). The BRCAness phenotype was significantly associated with large tumor size (>2 cm, P = .009), positive lymph nodes (P = .008), grade 3 tumor (P = .0001), high Ki-67 levels (P = .001), and basal-like breast cancers (P = .0001). Combined detections of BRCA1 promoter methylation and BRCA1-like genomic profile could identify more BRCAness cases in TNBCs. BRCA1 promoter methylation might rule out BRCA1 germline mutation in TNBCs. BRCAness was associated with aggressive clinicopathological features. These findings might have clinical values in hereditary breast cancer screening and target treatment of TNBCs.
一些散发性三阴性乳腺癌（TNBC）具有与 BRCA1/2 突变型乳腺癌相似的临床病理和分子特征，这种表型被描述为“BRCA 样”。在 TNBC 中鉴定 BRCA 样状态可以扩大铂盐和聚（腺苷二磷酸核糖）聚合酶抑制剂的靶群体。本研究的目的是评估 BRCA1/2 启动子甲基化和 BRCA1 样基因组谱来识别 BRCA 样状态的临床有效性，并评估其与 TNBC 临床病理特征的相关性。收集了 151 例原发性浸润性 TNBC 的福尔马林固定、石蜡包埋组织和新鲜组织。分别使用甲基化特异性多重连接依赖性探针扩增和多重连接依赖性探针扩增检测 BRCA1/2 启动子甲基化和 BRCA1 样基因组谱。通过定量逆转录聚合酶链反应评估 BRCA1/2 信使 RNA 表达。在 151 例患者中，38 例（25.2%）显示 BRCA1 启动子甲基化。在 124 例中，52 例（41.9%）具有 BRCA1 样多重连接依赖性探针扩增谱。BRCA 样表型的频率为 54.8%（68/124）。BRCA1 种系突变和 BRCA1 启动子甲基化是相互排斥的（P =.002）。BRCA 样表型与肿瘤较大（>2cm，P =.009）、淋巴结阳性（P =.008）、肿瘤分级 3 级（P =.0001）、高 Ki-67 水平（P =.001）和基底样乳腺癌（P =.0001）显著相关。BRCA1 启动子甲基化和 BRCA1 样基因组谱的联合检测可在 TNBC 中鉴定更多的 BRCA 样病例。BRCA1 启动子甲基化可能排除 TNBC 中的 BRCA1 种系突变。BRCA 样与侵袭性临床病理特征相关。这些发现可能在遗传性乳腺癌筛查和 TNBC 的靶向治疗中有临床价值。
