FGFR2c Mesenchymal Isoform Expression Is Associated with Poor Prognosis and Further Refines Risk Stratification...

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Endometrial cancer (EC) has common molecular subtypes, mismatch repair deficient (MMRd) and p53 wild-type (p53wt), with intermediate prognoses requiring better risk stratification.
• Fibroblast growth factor receptor 2 (FGFR2) isoform switching from FGFR2b to FGFR2c has been observed in other carcinomas.

Purpose of the Study:

• To investigate the potential of FGFR2c as a biomarker for risk stratification in endometrial cancer.
• To evaluate the prognostic value of FGFR2c expression in different molecular subtypes and risk groups of EC.

Main Methods:

• Development and optimization of a BaseScope RNA ISH assay for FGFR2c detection.
• Analysis of FGFR2c expression in a preliminary cohort (n=78) and a clinically annotated Vancouver cohort (n=465) of EC patients.
• Prognostic value assessment using Cox regression models.

Main Results:

• FGFR2c expression significantly correlated with shorter disease-specific survival (DSS) and progression-free survival (PFS) in endometrioid endometrial cancer (EEC, n=302).
• FGFR2c was a significant predictor of poorer outcomes in high-risk EEC, including grade 3 tumors and the European Society Medical Oncology (ESMO) high-risk group.
• In the MMRd subtype, FGFR2c expression was associated with significantly reduced PFS and DSS.

Conclusions:

• FGFR2c expression is an independent prognostic biomarker for EEC.
• FGFR2c can further stratify risk within grade 3 tumors, ESMO high-risk groups, and MMRd/p53wt subtypes.
• Incorporating FGFR2c into molecular subtyping can enhance risk stratification for EEC.