Purpose Activating FGFR2 mutations have been identified in ~ 10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort. Methods Tumors were collected as part of the GOG 210 clinical trial “Molecular Staging of Endometrial Cancer” where samples underwent rigorous pathological review and had more than three years of detailed clinical follow-up. DNA was extracted and four exons encompassing the FGFR2 mutation hotspots were amplified and sequenced. Results Mutations were identified in 144 of the 973 endometrioid ECs, of which 125 were classified as known activating mutations and were included in the statistical analyses. Consistent with FGFR2 having an association with more aggressive disease, FGFR2 mutations were more common in patients initially diagnosed with stage III/IV EC (29/170;17%) versus stage I/II EC (96/803; 12%; p = 0.07, Chi-square test). Additionally, incidence of progression (progressed, recurred or died from disease) was significantly more prevalent (32/125, 26%) among patients with FGFR2 mutation versus wild type (120/848, 14%; p < 0.001, Chi-square test). Using Cox regression analysis adjusting for known prognostic factors, patients with FGFR2 mutation had significantly (p < 0.025) shorter progression-free survival (PFS; HR 1.903; 95% CI 1.177–3.076) and endometrial cancer specific survival (ECS; HR 2.013; 95% CI 1.096–3.696). Conclusion In summary, our findings suggest that clinical trials testing the efficacy of FGFR inhibitors in the adjuvant setting to prevent recurrence and death are warranted.
Bibliographical noteFunding Information:
This study was supported by National Cancer Institute grants to PJG and PMP (R21 CA133295, P50 CA1342540) as well as to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), the GOG Tissue Bank (U10 CA27469, U24 CA114793, and U10 CA180868), and the NRG Oncology Group (U10 CA180822). PMP has been supported by an NHMRC career development fellowship. In addition, this research was supported in part by funds provided by the intramural research program of the National Cancer Institute, National Institutes of Health.
- Endometrial cancer