93P - A new platform for fast-track molecular stratification of endometrial carcinomas enabling timely treatment decisions in precision oncology

Background

Endometrial carcinomas (EC) are the most common gynecological cancer in the developed world. The original histopathology-based classification has been supplemented in the recent years by a molecular classification, based on the analysis of POLE mutation, microsatellite instability (MSI) and copy number variation. These markers have been used to develop prognostic risk groups with specific treatment options. Hence, the molecular stratification has been recommended internationally by different organizations and associations (e.g., ESMO, ESGO), allowing individualized treatment stratifications. Historically, these markers have been analyzed by various methods such as immunohistochemistry (IHC), Sanger sequencing and PCR-based fragment analysis. But the lack of single streamlined workflow has hampered the widespread adoption.

Methods

We developed three assays for discrimination of EC into ultramutated (POLE), hypermutated (MSI) and copy number high (CN high) phenotypes. CN high tumors are stratified based on molecular level with two newly identified biomarkers. We pre-characterized a patient cohort compromising of 41 samples, using IHC (MLH1, MSH2, MSH6, PMS2 and the surrogate marker TP53). Using our proprietary molecular analysis platform MODAPLEX, that unifies PCR and capillary gel electrophoresis, we analyzed this cohort with the three assays with a 4-hour turn-around time. The concordance was determined by calculation of the sensitivity.

Results

The concordance analysis of our MODAPLEX assays revealed a sensitivity of 0.923 (95% CI [0.781, 1.066]) for MSI compared to the IHC results and 0.833 (95% CI [0.622, 1.044]) for CN high compared to p53-IHC, respectively. We verified 100% of the mutations identified with the MODAPLEX POLE/POLD1 assay.

Conclusions

Overall, this study demonstrates a multi-gene/multi-marker testing workflow with complete molecular stratification for EC into a single streamlined, time- and cost-effective run. This approach will allow timely access to molecular-guided therapy for individual patients by enabling same day results, with a relative ease of implementation and fully integrated data analysis.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Biotype GmbH, Dresden, Germany.

Funding

Biotype GmbH, Dresden, Germany.

Disclosure

S. Walz, C. Schanzenbach, A. Aich, R. Weißbach, R. Braun, A. Hennig, J. Schoebel, S. Hofmann: Financial Interests, Institutional, Full or part-time Employment: Biotype GmbH.