Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Cancer Medicine, Jikei University Graduate School of Medicine, Tokyo, Japan.
J Gynecol Oncol. 2022 Nov;33(6):e82. doi: 10.3802/jgo.2022.33.e82. Epub 2022 Sep 27.
Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer.
This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors.
Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140-205] vs. 125 [IQR, 110-150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21-20.53; p=0.001).
In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.
叶酸受体α（FRα）是一种在多种实体瘤中表达的膜蛋白，但在正常细胞中表达有限。因此，FRα是癌症治疗的一个有吸引力的靶点。本研究旨在探讨 FRα 表达与宫颈癌临床病理特征和生存的关系。
本回顾性研究纳入了 2000 年至 2020 年期间在我院接受初次手术的宫颈癌患者。使用抗叶酸结合蛋白/FBP 抗体进行 FRα 免疫组织化学染色。FRα 阳性染色定义为≥5%的肿瘤染色，FRα 高表达定义为≥50%的肿瘤染色强度≥2+。使用多变量 Cox 回归分析评估 FRα 表达与生存的关系，调整了既定的预后因素。
共纳入 123 例患者，评估了 140 例肿瘤标本，包括 17 对原发和转移标本。组织学类型方面，67 例为鳞状细胞癌（SCC），56 例为非 SCC。所有原发肿瘤均为 FRα 阳性。高 FRα 表达率为 25%，且根据组织学类型有所不同（SCC 与非 SCC 相比，14.9%与 37.5%，p=0.004）。转移瘤中 FRα 表达显著高于原发瘤（170[IQR，140-205] vs. 125[IQR，110-150]，p=0.0006）。高 FRα 表达与总体生存较差显著相关（危险比，6.73；95%置信区间，2.21-20.53；p=0.001）。
在宫颈癌中，转移瘤中 FRα 表达升高，高表达与预后较差相关。本研究支持开发 FRα 靶向治疗晚期宫颈癌。
