741P - Comparison of the Idylla microsatellite instability (MSI) test with a gold standard MSI test and mismatch repair immunohistochemistry in endometrial cancer

Background

Determination of the molecular subtype of endometrial cancer has been shown to be prognostic and predictive and is therefore essential for treatment decisions and prognosis prediction in endometrial cancer. Therefore, assessment of mismatch repair protein (MMR) deficiency by immunohistochemistry (IHC) and sequential microsatellite instability (MSI) in cases with indeterminate protein expression status is part of routine diagnostics in the diagnosis of endometrial cancer. Several methods are available for MSI analysis.

Methods

We compared the Idylla™ MSI Assay (Biocartis) with our institutional MSI gold standard test (Bethesda panel) and with MMR IHC in a cohort of n=332 hysterectomy specimen of endometrioid adenocarcinomas of the corpus uteri (2008-2016). MSI tests were performed according to the manufacturer's recommendations (Idylla™) and a validated internal protocol (Bethesda panel). MMR IHC was analyzed using tissue microarrays, but repeated on whole slides in case of a negative internal control or a discrepancy with the MSI test. The Idylla™ MSI results were compared with the Bethesda MSI results and the MMR-IHC.

Results

In our cohort of n=332 endometrioid endometrial cancer cases, MMR IHC, Idylla™ MSI and gold standard (Bethesda) MSI test results were evaluable in all cases, n=325, and n=324, respectively. N=87/332 (26.2%) had MMR deficiency (MMRd) with n=78/332 (23.5%) showing MLH1/PMS2 loss. The Idylla™ MSI assay revealed MSI in n=68/325 (20.9%) cases. Idylla™ results agreed with MMR IHC results in n=303/325 cases (overall percentage agreement (OPA)=93.2%; Kappa= 0.814). Bethesda results were consistent with MMR IHC results in n=310/324 cases (OPA=95.7%; Kappa= 0.884). Both Idylla™ and Bethesda MSI results were available for n=322/332 cases (97.0%) with n=308/322 concordant cases. OPA between the two MSI test methods was therefore 95.65% (Kappa= 0.874).

Conclusions

Idylla™ MSI showed a very high OPA with the gold standard MSI test and with MMR IHC. In view of its short turnaround time and ease of use, this test could therefore be an excellent alternative for MSI testing in endometrial cancer, even with old tissue samples.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Biocartis provided the cartridges free of charge.

Disclosure

R. Erber: Financial Interests, Institutional, Research Funding: Biocartis; Financial Interests, Personal, Invited Speaker: AstraZeneca. I. Unser, A. Hartmann, R. Stöhr: Financial Interests, Institutional, Research Funding: Biocartis. All other authors have declared no conflicts of interest.