Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Bax HJ

PROVIDER: S-EPMC9902484 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Bax Heather J HJ Chauhan Jitesh J Stavraka Chara C Santaolalla Aida A Osborn Gabriel G Khiabany Atousa A Grandits Melanie M López-Abente Jacobo J Palhares Lais C G F LCGF Chan Wah Hak Charleen C Robinson Alexandra A Pope Amy A Woodman Natalie N Naceur-Lombardelli Cristina C Malas Sadek S Coumbe Jack E M JEM Nakamura Mano M Laddach Roman R Mele Silvia S Crescioli Silvia S Black Anna M AM Lombardi Sara S Canevari Silvana S Figini Mariangela M Sayasneh Ahmad A Tsoka Sophia S FitzGerald Kevin K Gillett Cheryl C Pinder Sarah S Van Hemelrijck Mieke M Kristeleit Rebecca R Ghosh Sharmistha S Montes Ana A Spicer James J Karagiannis Sophia N SN Josephs Debra H DH

British journal of cancer 20221119 2

<h4>Background</h4>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.<h4>Methods</h4>We evaluated sFRα longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FRα expression status by immunohistrochem ...[more]

PMID: 36402875

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Project description:Complete resection of tumor lesions in advanced stage ovarian cancer patients is of utmost importance, since the extent of residual disease after surgery strongly affects survival. Intraoperative imaging may be useful to improve surgery in these patients. Farletuzumab is a humanized IgG1 antibody that specifically recognizes the folate receptor alpha (FRα). Labeled with a radiolabel and a fluorescent dye, farletuzumab may be used for the intraoperative detection of ovarian cancer lesions. The current aim is to demonstrate the feasibility of FRα-targeted dual-modality imaging using 111In-farletuzumab-IRDye800CW in an intraperitoneal ovarian cancer model. Biodistribution studies were performed 3 days after injection of 3, 10, 30, or 100 μg of 111In-farletuzumab-IRDye800CW in mice with subcutaneous IGROV-1 tumors (5 mice per group). In mice with intraperitoneal IGROV-1 tumors the nonspecific uptake of 111In-farletuzumab-IRDye800CW was determined by coinjecting an excess of unlabeled farletuzumab. MicroSPECT/CT and fluorescence imaging were performed 3 days after injection of 10 μg of 111In-farletuzumab-IRDye800CW. FRα expression in tumors was determined immunohistochemically. Optimal tumor-to-blood-ratios (3.4-3.7) were obtained at protein doses up to 30 μg. Multiple intra-abdominal tumor lesions were clearly visualized by microSPECT/CT, while uptake in normal tissues was limited. Fluorescence imaging was used to visualize and guide resection of superficial tumors. Coinjection of an excess of unlabeled farletuzumab significantly decreased tumor uptake of 111In-farletuzumab-IRDye800CW (69.4 ± 27.6 versus 18.3 ± 2.2% ID/g, p < 0.05). Immunohistochemical analyses demonstrated that the radioactive and fluorescent signal corresponded with FRα-expressing tumor lesions. FRα-targeted SPECT/fluorescence imaging using 111In-farletuzumab-IRDye800CW can be used to detect ovarian cancer in vivo and could be a valuable tool for enhanced intraoperative tumor visualization in patients with intraperitoneal metastases of ovarian cancer.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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