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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 (FRα) and the soluble receptor (sFRα) is measurable in blood. Here we investigated sFRα as a potential biomarker.

METHODS

We evaluated sFRα longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FRα expression status by immunohistrochemistry. The impact of free FRα on the efficacy of anti-FRα treatments was evaluated by an antibody-dependent cellular cytotoxicity assay.

RESULTS

Membrane and/or cytoplasmic FRα staining were observed in 52.7% tumours from 316 ovarian cancer patients with diverse histotypes. Circulating sFRα levels were significantly higher in patients, compared to healthy volunteers, specifically in patients sampled prior to neoadjuvant and palliative treatments. sFRα was associated with FRα cell membrane expression in the tumour. sFRα levels decreased alongside concurrent tumour burden in patients receiving standard therapies. High concentrations of sFRα partly reduced anti-FRα antibody tumour cell killing, an effect overcome by increased antibody doses.

CONCLUSIONS

sFRα may present a non-invasive marker for tumour FRα expression, with the potential for monitoring patient response to treatment. Larger, prospective studies should evaluate FRα for assessing disease burden and response to systemic treatments.

背景

卵巢癌的生存率仍然很差，监测和预测治疗反应可能受益于额外的标志物。卵巢癌经常过度表达叶酸受体 alpha（FRα），并且可以在血液中测量可溶性受体（sFRα）。在这里，我们研究了 sFRα 作为一种潜在的生物标志物。

方法

我们通过免疫组织化学评估了 sFRα 在新辅助、辅助和姑息治疗前后的纵向变化，以及肿瘤 FRα 表达状态。通过抗体依赖性细胞毒性测定评估游离 FRα 对抗 FRα 治疗效果的影响。

结果

在 316 名具有不同组织学类型的卵巢癌患者的 52.7%肿瘤中观察到膜和/或细胞质 FRα 染色。与健康志愿者相比，患者的循环 sFRα 水平明显更高，特别是在接受新辅助和姑息治疗前采样的患者中。sFRα与肿瘤细胞表面的 FRα 表达相关。在接受标准治疗的患者中，sFRα 水平随肿瘤负荷的同步降低而降低。sFRα 的高浓度部分降低了抗 FRα 抗体对肿瘤细胞的杀伤作用，这种作用可以通过增加抗体剂量来克服。