Utilization of unlabeled probes for the detection of fibroblast growth factor receptor 2 exons 7 and 12 mutations in endometrial carcinoma.

Background: Endometrial adenocarcinomas are associated with a variety of molecular abnormalities including microsatellite instability, Kirsten rat sarcoma viral oncogene homolog mutations, and phosphatase and tensin homolog inactivation. Recently, mutations in fibroblast growth factor receptor 2 (FGFR2) have been described but their frequency and clinicopathologic characteristics are incompletely known.

Methods: To determine the frequency of mutations in FGFR2 exons 7 and 12, 43 adenocarcinomas of the endometrium were studied by high-resolution melting analysis utilizing unlabeled probes and sequencing.

Results: Three of 43 (7%) endometrial carcinomas harbored FGFR2 exon 7 mutations. All 3 mutations were S252W and occurred in endometrioid (type I) adenocarcinomas. Direct sequencing indicated that 2 of the S252W mutations were heterozygous, whereas 1 was presumably homozygous. No FGFR2 mutations were detected in exon 12.

Conclusions: FGFR2 mutations occur in approximately 7% of adenocarcinomas of the endometrium. Only carcinomas of an endometrioid morphology contain FGFR2 mutations, and in our series all were S252W. FGFR2 exons 7 and 12 unlabeled DNA probes allow for easy screening of endometrial carcinoma for the 2 most common FGFR2 mutations (S252W and N550K). Identification of these mutations may have important implications in directed molecular therapy.