FGFR2 mutations are associated with poor outcomes in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.
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.



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.



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).



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.
Queensland University of Technology (QUT) at the Translational Research Institute, Brisbane, Australia.
Yvette W
YW
Jeske
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA.
Shamshad
S
Ali
Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Sara A
SA
Byron
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
Feng
F
Gao
Gynecologic Oncology, The Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Robert S
RS
Mannel
University of Minnesota Medical Center - Fairview, Minneapolis, MN, USA.
Rahel G
RG
Ghebre
Gynecologic Oncology, Women and Infants Hospital, Providence, RI, USA.
Paul A
PA
DiSilvestro
Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Shashikant B
SB
Lele
Obstetrics and Gynecology, Stony Brook University Hospital, Stony Brook, NY, USA.
Michael L
ML
Pearl
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, USA.
Amy P
AP
Schmidt
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA.
Heather A
HA
Lankes
GOG Tissue Bank/NRG Oncology Biospecimen Bank - Columbus, Biopathology Center, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Nilsa C
NC
Ramirez
Department of Laboratory Medicine, University of Toronto, ON, M5G2C, CANADA.
Golnar
G
Rasty
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, USA.
Matthew
M
Powell
Department of Obstetrics and Gynecology, The Ohio State University and James Comprehensive Cancer Center, Columbus, OH, USA.
Paul J
PJ
Goodfellow
Queensland University of Technology (QUT) at the Translational Research Institute, Brisbane, Australia; Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA. Electronic address: pamela.pollock@qut.edu.au.
Pamela M
PM
Pollock
D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D009367:Neoplasm Staging; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*
D004273:DNA, Neoplasm; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
Endometrial cancer; FGFR2; Mutation; Outcome; Prognosis