Folate receptor alpha in ovarian cancer tissue and patient serum is associated with disease burden and treatment outcomes

Background Survival rates for ovarian cancer remain poor, and monitoring and prediction of therapeutic response may benefit from additional markers. Ovarian cancers frequently overexpress Folate Receptor alpha (FR alpha) and the soluble receptor (sFR alpha) is measurable in blood. Here we investigated sFR alpha as a potential biomarker. Methods We evaluated sFR alpha longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FR alpha expression status by immunohistrochemistry. The impact of free FR alpha on the efficacy of anti-FR alpha treatments was evaluated by an antibody-dependent cellular cytotoxicity assay. Results Membrane and/or cytoplasmic FR alpha staining were observed in 52.7% tumours from 316 ovarian cancer patients with diverse histotypes. Circulating sFR alpha levels were significantly higher in patients, compared to healthy volunteers, specifically in patients sampled prior to neoadjuvant and palliative treatments. sFR alpha was associated with FR alpha cell membrane expression in the tumour. sFR alpha levels decreased alongside concurrent tumour burden in patients receiving standard therapies. High concentrations of sFR alpha partly reduced anti-FR alpha antibody tumour cell killing, an effect overcome by increased antibody doses. Conclusions sFR alpha may present a non-invasive marker for tumour FR alpha expression, with the potential for monitoring patient response to treatment. Larger, prospective studies should evaluate FR alpha for assessing disease burden and response to systemic treatments.

Automated summary

This study investigated the potential use of sFR alpha as a biomarker for ovarian cancer. The results showed that sFR alpha levels were significantly higher in patients compared to healthy volunteers and decreased alongside tumor burden during treatment. Additionally, high concentrations of sFR alpha reduced the effectiveness of anti-FR alpha antibodies, but this effect could be overcome by increasing antibody doses.