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FGFR2 alterations in endometrial carcinoma
Sonia Gatius1, Ana Velasco, Ainara Azueta
1Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
Summary
Fibroblast growth factor receptor 2 (FGFR2) acts as a tumor suppressor in normal endometrium but functions as an oncogene in endometrial cancer. FGFR2 inhibition may be a therapeutic target for endometrial carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Gynecologic Pathology
Background:
- Fibroblast growth factor receptor 2 (FGFR2) is crucial for embryogenesis and tissue homeostasis.
- FGFR2 mutations are found in 10-12% of endometrial carcinomas, suggesting its role in cancer development.
- Targeting FGFR2 inhibition presents a potential therapeutic strategy for endometrial carcinoma.
Purpose of the Study:
- To investigate the expression patterns and mutational status of FGFR2 in normal and cancerous endometrial tissues.
- To correlate FGFR2 expression with clinicopathological features of endometrial carcinoma.
- To elucidate the dual role of FGFR2 in endometrial physiology and carcinogenesis.
Main Methods:
- FGFR2 immunostaining was performed on tissue microarrays of normal endometrium (60 samples) and endometrial carcinomas (95 and 62 samples).
- Expression levels were correlated with various clinicopathological parameters and molecular markers (PTEN, RASSF1A, hormone receptors, Ki67, etc.).
- FGFR2 gene mutations were analyzed in 31 endometrial carcinoma samples using PCR and direct sequencing.
Main Results:
- FGFR2 expression was higher in the secretory phase of normal endometrium and inversely correlated with Ki67, suggesting a tumor-suppressor role.
- Cytoplasmic FGFR2 expression was higher in endometrial carcinoma compared to atrophic endometrium but lower than in normal cycling endometrium.
- Endometrioid endometrial carcinomas exhibited higher FGFR2 expression than non-endometrioid types, with decreased expression in Grade III compared to Grade II.
- Two missense mutations (S252W and N549K) were identified in 6.45% of the analyzed samples.
Conclusions:
- FGFR2 exhibits a dual role in the endometrium: acting as a tumor suppressor in normal tissue and an oncogene in endometrial carcinoma.
- FGFR2 expression patterns differ between normal and cancerous endometrium and vary by histological subtype and grade.
- The findings support FGFR2 as a potential therapeutic target in endometrial carcinoma.
