Johnson Jeff, Choi Michael, Dadmanesh Farnaz, Han Bingchen, Qu Ying, Yu-Rice Yi, Zhang Xiao, Bagaria Sanjay, Taylor Clive, Giuliano Armando E, Amersi Farin, Cui Xiaojiang
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Oncotarget. 2016 Nov 15;7(46):75729-75738. doi: 10.18632/oncotarget.12370.
Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been identified as a specific marker expressed in BLBC in general breast cancer cohorts. We examined an institutional cohort of breast cancer patients with germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in 5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib.
在遗传性乳腺癌基因BRCA1和BRCA2背景下发生的乳腺癌，最常分别被归类为基底样乳腺癌（BLBC）或管腔型乳腺癌。BLBC是一种侵袭性乳腺癌亚型，与肝转移和肺转移相关，预后比其他亚型差，化疗是其唯一的全身治疗方法。多种免疫组化标志物用于识别基底样亚型，包括雌激素受体α、孕激素受体和人表皮生长因子受体2的缺失。叉头框C1（FOXC1）已被确定为一般乳腺癌队列中BLBC中表达的一种特异性标志物。我们研究了一组患有种系BRCA1（n = 46）和BRCA2（n = 35）突变的乳腺癌患者，发现免疫组化染色中FOXC1的表达与BRCA1与BRCA2突变相关[30/46对6/35]。在BRCA1突变肿瘤中，FOXC1在28/31例BLBC肿瘤和2/13例非BLBC肿瘤中表达；在BRCA2突变肿瘤中，FOXC1在5/5例BLBC肿瘤和1/30例非BLBC肿瘤中表达。在BRCA1突变型乳腺癌的细胞培养模型中，FOXC1与增殖增加相关，可能作为对奥拉帕利PARP抑制剂治疗敏感性的标志物。
