P88 Analysis of 93 patients with endometrial cancer using the PROMISE classification and additional genetic analyses for MSI and POLE-EDM

Introduction/Background Recent research has distinguished various molecular classifications for endometrial carcinoma (EC). The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMise, Talhouk, BJC 2015,113:299) classification consists of immunohistochemistry (IHC) (p53 and mismatch repair proteins) and PCR sequencing for Polymerase Epsylon-Extracellular-Domain-Mutations (POLE-EDM). Methodology Ninety-three consecutive endometrial cancer patients, diagnosed between March 2017 and November 2018, were subjected to molecular and immunohistochemical analyses, according to ProMise. IHC for p53 and the mismatch repair proteins (MLH1, PMS2, MSH6 and PMS2) was performed. All patients were also tested for POLE-EDM using PCR, followed by Sanger sequencing (exon 9, 11, 13 and 14). In addition to the ProMise testing, all tumors and corresponding normal tissue of patients with mismatch repair deficient staining on IHC, were tested with PCR using the Microsatellite Instability (MSI) kit (MSI analysis system, Promega). Hypermethylation of MLH1 promotor and the presence of the BRAF p.V600E missense mutation was tested with (methylation specific) multiplex ligation dependent probe amplification. Results FIGO classification was stage IA(n=45), IB(n=17)) II(n=8), III(n=17) and IV(n=6). Classification according to histological type is presented in table 1. Of the 28 patients with MMR-D (Mismatch Repair-Deficiency) on IHC, 22(79%) showed hypermethylation as the probable cause of MMR-D. The remaining 6 patients were referred for germline analysis of Lynch syndrome. Five patients carried a pathogenic germline mutation in one of the mismatch repair genes: MSH6(n=3), PMS2(n=1), MLH1(n=1). In one patient no germline mutation was identified, hypothesizing a somatic cause. POLE-EDM was identified in 6 (6%) patients. Double positive status (POLE-EDM+MMR-D or POLE-EDM+p53 abnormal) was observed in 4 patients (4%) (table1). Conclusion The ProMise classification proved to be an efficient and easily implementable system. In the group with MMR-D, hypermethylation was the cause in 79%. POLE-EDM was identified in 6% of the patients, but its role needs to be clarified in non-endometrioid tumors. Disclosure Nothing to disclose.