From the Department of Pathology, West China Hospital, Sichuan University, Chengdu, China (Drs Zhang, Chen, Wei, and Bu); RTI Health Solution, Research Triangle Park, North Carolina (Dr Wang); Biocare, Inc, Concord, California (Drs Tacha and Bremer); the Departments of Surgical Oncology (Drs Li and Skinner) and Pathology (Drs Hicks and Tang), University of Rochester Medical Center, Rochester, New York; the Department of Pathology, Luzhou Medical College, Luzhou, China (Dr Xiao); and the Department of Pathology, Japan-China Friendship Hospital, Beijing, China (Dr Da).
Arch Pathol Lab Med. 2014 Jul;138(7):890-5. doi: 10.5858/arpa.2013-0309-OA. Epub 2013 Sep 13.
Folate receptor α (FRA) has been shown to be selectively expressed in several types of human cancer, including breast cancer. Currently, several FRA target therapies are under intensive study.
To investigate the expression pattern of FRA in a large cohort of patients with breast cancer and analyze its relationship with different clinicopathologic features, with expression of several key biomarkers, and with clinical outcome.
Four hundred forty-seven cases of infiltrating ductal carcinoma diagnosed between 1997 and 2008 at the University of Rochester Medical Center were identified and reviewed, and 25 blocks of tissue microassays were constructed. The association between expression of FRA and clinicopathologic features; expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67; and clinical outcome of these tumors were evaluated.
The expression of FRA was significantly associated with tumors with high histologic grade, higher nodal stages, ER/PR negativity, and high proliferative activity (Ki-67 ≥ 15%), and was independent of HER2/neu overexpression. In all, 74% of ER/PR-negative and 80% of triple-negative breast cancers expressed FRA. The expression of FRA was significantly associated with a worse disease-free survival.
Our data demonstrate that a significant subgroup of ER/PR-negative and triple-negative breast cancers express FRA, and its expression is associated with worse clinical outcome.
叶酸受体α（FRA）已被证明在多种类型的人类癌症中选择性表达，包括乳腺癌。目前，几种 FRA 靶向治疗正在深入研究中。
研究 FRA 在大量乳腺癌患者中的表达模式，并分析其与不同临床病理特征、关键生物标志物表达以及临床结局的关系。
在罗彻斯特大学医学中心，我们鉴定和回顾了 1997 年至 2008 年期间诊断的 447 例浸润性导管癌病例，并构建了 25 个组织微阵列。评估 FRA 表达与临床病理特征、雌激素受体（ER）、孕激素受体（PR）、HER2/neu 和 Ki-67 表达以及这些肿瘤的临床结局之间的关系。
FRA 的表达与组织学分级较高、淋巴结分期较高、ER/PR 阴性和增殖活性较高（Ki-67≥15%）的肿瘤显著相关，并且与 HER2/neu 过表达无关。在所有 ER/PR 阴性和三阴性乳腺癌中，有 74%和 80%表达 FRA。FRA 的表达与无病生存显著相关。
我们的数据表明，相当一部分 ER/PR 阴性和三阴性乳腺癌表达 FRA，其表达与更差的临床结局相关。
