147P - Comparison of immune-checkpoint inhibitor therapy predictive marker tests microsatellite instability (MSI) and mismatch-repair deficiency (dMMR)

Background

The tumor-agnostic indication of immune checkpoint inhibitors to treat cancers with mismatch repair deficiency (dMMR)/microsatellite instability (MSI) increased the demand for such tests beyond Lynch syndrome. International guideline recommendations accept immunohistochemistry (IHC) for dMMR or molecular techniques (PCR, NGS) for MSI status determination tests equal, although there are scattered reports contradicting to this presumption.

Methods

We have directly compared four protein MMR immunohistochemistry to MSI Pentaplex PCR tests in a large cancer patient cohort (n=1306) of our diagnostic center where the two tests have been run parallel in 703 cases.

Results

We have found a high discrepancy rate (19.3%) of the two tests, independent of the tumor types. The MSI PCR sensitivity for MMR IHC status was found to be low (41.1%) with relatively low positive (91.6%) and negative (80.5%) predicting values. Therefore, the correlation of the two tests was low (kappa<0.7). During analysis of the possible contributing factors of this poor performance, we have excluded low tumor percentage of the samples, but identified dMMR phenotypes (classic versus non-classic or unusual) as possible contributors, since the sensitivities of PCR were very different (62.7%, 37.2%, 5.1%, respectively).

Conclusions

Our study challenges the perception that the MSI PCR and MMR IHC are equal predictive tests which might have clinical relevance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.