High expression of folate receptor alpha is associated with poor prognosis in patients with cervical cancer

• Published in: Journal of gynecologic oncology Vol. 33; no. 6; pp. 1 - 12
• Main Authors: Shu Yazaki, Yuki Kojima, Hiroshi Yoshida, Shigemasa Takamizawa, Rui Kitadai, Tadaaki Nishikawa, Tatsunori Shimoi, Kazuki Sudo, Ayumi Saito, Hitomi Sumiyoshi Okuma, Maki Tanioka, Emi Noguchi, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Yasuhiro Fujiwara, Yuichiro Ohe, Kan Yonemori
• Format: Journal Article
• Language: Korean
• Published: 대한부인종양학회 01-11-2022
• Subjects: Biomarkers; Cervical Cancer; Folate Receptor Alpha
• ISSN: 2005-0380

Objective: 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.
Methods: 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.
Results: 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).
Conclusion: 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.