Zannoni Gian Franco, Santoro Angela, d'Amati Antonio, D'Alessandris Nicoletta, Scaglione Giulia, Padial Urtueta Belen, Valente Michele, Narducci Nadine, Addante Francesca, Spadola Saveria, Bragantini Emma, Angelico Giuseppe
Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Pathology Institute, Catholic University of Sacred Heart, 00168 Rome, Italy.
Int J Mol Sci. 2025 May 29;26(11):5222. doi: 10.3390/ijms26115222.
Folate receptor alpha (FRα), a glycosylphosphatidylinositol-anchored glycoprotein encoded by the gene, plays a crucial role in folate transport during cell growth and development. While minimally expressed in most normal adult tissues, FRα is frequently overexpressed in several epithelial malignancies, particularly in high-grade serous ovarian carcinoma. An immunohistochemical (IHC) evaluation of FRα expression using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay is now approved as a companion diagnostic for selecting patients eligible for mirvetuximab soravtansine, an FRα-targeted antibody-drug conjugate. Clinical trials such as SORAYA and MIRASOL have demonstrated significant clinical benefit in platinum-resistant epithelial ovarian cancer patients with high FRα expression (≥75% of tumor cells with moderate to strong membrane staining). This review summarizes the biological significance of FRα in ovarian cancer progression, its predictive value for targeted therapy, and the technical aspects of IHC assessment, including scoring interpretation and pre-analytical variables. We also discuss heterogeneity in FRα expression across histological subtypes and tumor sites, as well as the impact of archival versus fresh tissue. Understanding FRα expression patterns across histologic subtypes and tissue samples is critical for optimizing clinical decision-making and expanding the role of FRα-targeted therapies in gynecologic oncology.
叶酸受体α（FRα）是一种由该基因编码的糖基磷脂酰肌醇锚定糖蛋白，在细胞生长和发育过程中的叶酸转运中起关键作用。虽然在大多数正常成人组织中表达极少，但FRα在几种上皮性恶性肿瘤中经常过度表达，尤其是在高级别浆液性卵巢癌中。使用VENTANA FOLR1（FOLR1-2.1）RxDx检测法对FRα表达进行免疫组织化学（IHC）评估，现已被批准作为一种伴随诊断方法，用于选择适合接受mirvetuximab soravtansine（一种靶向FRα的抗体药物偶联物）治疗的患者。SORAYA和MIRASOL等临床试验已证明，对于FRα高表达（≥75%的肿瘤细胞呈中度至强膜染色）的铂耐药上皮性卵巢癌患者具有显著的临床益处。本综述总结了FRα在卵巢癌进展中的生物学意义、其对靶向治疗的预测价值以及IHC评估的技术方面，包括评分解读和分析前变量。我们还讨论了FRα表达在不同组织学亚型和肿瘤部位的异质性，以及存档组织与新鲜组织的影响。了解FRα在不同组织学亚型和组织样本中的表达模式对于优化临床决策以及扩大FRα靶向治疗在妇科肿瘤学中的作用至关重要。
