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

Objective: Folate receptor alpha (FR mu) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FR alpha is an attractive target for cancer treatment. This study aimed to investigate the relationship between FR alpha 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 FR alpha was performed using an anti-folate-binding protein/FBP antibody. FR alpha-positive staining was defined as >= 5% of tumor staining and FR alpha-high as >= 50% tumor staining with >= 2+ intensity. The association between FR alpha 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 FR alpha-positive. High FR alpha 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). FR alpha expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140-205] vs. 125 [IQR, 110-150], p=0.0006). High FR alpha 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, FR alpha expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FR alpha-targeted therapy for advanced cervical cancer.