Abstract 1125P
Background
Folate receptor-α-1 (FOLR1) encodes a membrane protein, FRα, that is overexpressed in up to 80% of epithelial ovarian cancers (EOC) while absent from normal ovarian tissue. This mutual exclusivity of FRα expression has garnered interest in FRα as a therapeutic target. Several FRα targeted therapies are under clinical investigation, underscoring the need for a robust and reproducible assay to detect expression of FRα to ensure accurate patient selection. Here, we describe the analytical performance of a FRα immunohistochemical (FOLR1 IHC) assay in EOC.
Methods
FFPE EOC specimens were stained with the FOLR1 IHC Assay and scored by pathologists for percent tumor cell membrane staining at weak, moderate, and strong intensities. For repeatability and intermediate precision studies, the case-level modal staining result was determined for each specimen and the results from replicate slides stained under each test condition were compared and evaluated for agreement to the case-level modal staining result. For inter- and intra-reader precision studies, pathologists (N=3) evaluated 100 cases and were compared to each other for agreement.
Results
All analytical repeatability and intermediate precision assessments showed > 98% overall percent agreement (OPA)*. Intra-reader precision assessment showed a 97% OPA and inter-reader precision showed a 93.3% OPA. The results are summarized in the table. Table: 1125P
| Study | PPA (95% CI) | NPA (95% CI) | OPA (95% CI) |
| Inter-instrument | 100 (95, 100) | 99 (97,100) | 99 (99, 100) |
| Inter-day | 99 (97, 100) | 99 (97, 100) | 99 (97, 100) |
| Within-run | 99 (98, 100) | 99 (98, 100) | 99 (98, 100) |
| Inter-antibody | 100 (95, 100) | 100 (95, 100) | 100 (97, 100) |
| Inter-detection | 99 (97, 100) | 100.0 (95, 100) | 99 (99, 100) |
| APA (95% CI) | ANA (95% CI) | OPA (95% CI) | |
| Inter-reader | 93 (89, 97) | 93 (90, 97) | 93 (90, 97) |
| Intra-reader | 97 (95, 99) | 97 (95, 99) | 97 (95, 99) |
APA = Average positive agreement ANA = Average negative agreement PPA = Positive percent agreement NPA = Negative percent agreement *A 75% TC at moderate and/or strong intensities was considered positive
Conclusions
The FOLR1 IHC Assay is a robust and reproducible assay for detecting FRɑ expression in EOC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Roche Tissue Diagnostics.
Funding
Roche Tissue Diagnostics.
Disclosure
R. James, B. Admire, T. Sisserson, Z. Cai, M. Dumas, L.J. Inge, J. Baumann, P. Towne, D. Dalvi, E.A. ElGabry: Financial Interests, Institutional, Full or part-time Employment: Roche Tissue Diagnostics.