Utility of multi-gene panel testing with next generation sequencing in women with endometrial cancer.

Abstract

5588 Background: Lynch syndrome (LS) accounts for 2-6% of all endometrial cancers (EC), and women with a germline mutation in the mismatch repair (MMR) genes ( MLH1, MSH2, MSH6, and PMS2) have an average lifetime risk of EC of 40%. As with breast and ovarian cancer syndromes, there are likely other genes implicated in the development of EC outside of the MMR genes. Multi-gene panel testing (MGPT) with next generation sequencing (NGS) allows for simultaneous analysis of numerous genes.We sought to evaluate the characteristics and incidence of gene mutations in women with newly diagnosed EC. Methods: We conducted a review of EC patients diagnosed from 6/2013 to 12/2016 who had MGPT at our institution. Demographics, family history, genetic testing results, and tumor characteristics were collected and analyzed using χ2 tests. Results: Of the 129 patients who had MGPT, 13 (10%) had a mutation and only 5 (38%) were in patients < 50 years old. The median age of EC diagnosis is 55 (31-100) years and median BMI = 27.5 (21-59). Majority were stage 1, 76 (59%) and grade 1, 50 (39%). Patients with additional primary cancers, breast or colon were not more likely to have a mutation. However, patients with a family history of gynecologic cancer were more likely to have a mutation identified, 10 (77%) mutation vs no mutation 34 (29%), p = 0.003. Among all patients tested, 8 (6%) had a mutation in LS genes, and 6 (5%) had mutations in other genes ( BRCA1, BRCA2, RAD51C, MUTYH, CHEK2); 1 (0.8%) had both MSH2 and CHEK2 mutation. Three patients had prior testing for breast cancer; 2 were found to have a BRCA1/ 2 mutation and the other was on Tamoxifen and BRCA negative. IHC was performed on 7 of 13 patients, and 5 (71%) had a loss of MMR protein expression. Variants of uncertain significance were noted in 35/129 (27%) of patients tested. Conclusions: Majority of EC patients with a mutation detected with NGS were > age 50. We identified additional new mutations in non-LS genes including, CHEK2, RAD51C, and MUYTH with MGPT. These accounted for 29% of the mutations and would have not been not detected using classic LS gene testing. These genes are implicated in breast, ovary or colon cancer. MGPT testing is feasible and useful in identifying additional actionable gene mutations.