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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Detecting FR-⍺ Expression Level in Cytology Effusion Specimens From Ovarian Cancer and Comparing It With Tissue
Yadan Ma1, Xiaofei Yu2, Xiaohong Duan1
1Department of Pathology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
Background:
Folate receptor-⍺ (FR-⍺) is an attractive target for targeted therapy. Mirvetuximab soravtansine (MIRV) has been approved by the United States Food and Drug Administration (FDA) for treating adult patients with FR-⍺ positive, platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Therefore, identifying and detecting FR-⍺ has become an essential part of precision medicine. This study aimed to evaluate the feasibility of detecting FR-⍺ protein expression in serous cavity effusions using cell blocks (CBs) and compare the results with surgical pathology biopsy or resection specimens. Furthermore, we investigated potential variations in FR-⍺ expression pre- and post-chemotherapy.
Methods:
Immunohistochemical (IHC) staining of FR-⍺ was performed on the serous cavity effusion specimens from 35 patients with epithelial ovarian cancer, along with matched surgical pathological (SP) biopsy or resection specimens, following the manufacturer's guidelines for IHC analysis.
Results:
Positive staining was observed in 30 (85.7%) and 32 (91.4%) serous cavity effusion CB and tissue samples, respectively. A total of 31 (88.5%) tissue and 28 (80%) effusion CB samples exhibited moderate-to-strong FR-⍺ expression in at least 25% of tumor cells. A cutoff of 25% for FR-⍺ expression positivity was used to demonstrate high concordance (96.4%) between cytology CBs and tissue specimens. We recommend a cutoff of 75% viable tumor cells with moderate-to-strong membrane staining as "positive" in CBs for greater reliability, which aligns with FDA-approved criteria. A reasonable consistency was observed in FR-⍺ expression between the pre-treatment serous cavity effusion CB specimens and the new biopsy specimens obtained after multiline treatment.
Conclusion:
We demonstrated that serous effusion CB specimens may be effective for FR-⍺ biomarker detection; FR-⍺ maintains stable expression pre- and post-chemotherapy, and patients can benefit from MIRV.
Insights
Detecting folate receptor-alpha (FR-α) in serous effusions using cell blocks is feasible and reliable for ovarian cancer patients. FR-α expression remains stable after chemotherapy, supporting targeted therapy with mirvetuximab soravtansine (MIRV).
Area of Science:
- Oncology
- Pathology
- Precision Medicine
Background:
- Folate receptor-alpha (FR-α) is a key target for novel cancer therapies.
- Mirvetuximab soravtansine (MIRV) is FDA-approved for FR-α-positive platinum-resistant ovarian cancer.
- Accurate FR-α detection is crucial for guiding treatment decisions in precision medicine.
Purpose of the Study:
- To assess the feasibility of detecting FR-α protein expression in serous cavity effusions via cell blocks (CBs).
- To compare FR-α detection results from CBs with traditional surgical pathology specimens.
- To investigate the stability of FR-α expression before and after chemotherapy.
Main Methods:
- Immunohistochemical (IHC) staining for FR-α was performed on 35 epithelial ovarian cancer serous cavity effusion CB specimens.
- Matched surgical pathology (SP) biopsy or resection specimens were used for comparison.
- Manufacturer's guidelines for IHC analysis were strictly followed.
Main Results:
- High concordance (96.4%) was observed between FR-α expression in cytology CBs and tissue specimens using a 25% positivity cutoff.
- Moderate-to-strong FR-α expression was detected in 85.7% of CBs and 91.4% of tissue samples.
- Consistent FR-α expression was noted between pre-treatment CBs and post-chemotherapy biopsy specimens.
Conclusions:
- Serous effusion CBs are effective for FR-α biomarker detection in ovarian cancer.
- FR-α expression is stable pre- and post-chemotherapy, validating its utility as a persistent biomarker.
- These findings support the use of FR-α testing in CBs for patient selection for MIRV therapy.

