PhD Scientific Days 2024

Pathological and Oncological Sciences I.

Microsatellite instability (MSI) and mismatch-repair deficiency (dMMR) testing as positive predictive factors for immune-checkpoint inhibitor therapy

Előadó neve

Nádorvári, Maja Lilla

Neptun code

GUU8IR

Előadó munkahelye

Semmelweis Egyetem Patológiai Igazságügyi és Biztosítás Orvostani Intézet

Előadó telefonszáma

06202397829

Előadó e-mail címe

majanadorvari@gmail.com

Az előadás címe

Microsatellite instability (MSI) and mismatch-repair deficiency (dMMR) testing as positive predictive factors for immune-checkpoint inhibitor therapy

Szerző(k) neve és munkahelye

Nádorvári Maja Lilla¹, Prof. Dr. Tímár József¹, Dr. Kenessey István¹, Prof Dr. Kiss András¹, Dr Barbai Tamás¹, Prof. Dr. Kulka Janina¹

1: Semmelweis Egyetem Patológiai Igazságügyi és Biztosítás Orvostani Intézet

Bemutatás módja

Szóbeli

Szekció

Pathological and Oncological Sciences I.

Language of the presentation

Hungarian

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Introduction: 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 IHC for dMMR or molecular techniques (PCR, NGS) for
MSI status determination tests equal, although there are scattered reports contradicting to this presumption.

Aims: Our goal was to directly compare four protein MMR IHC to MSI Pentaplex PCR test in a large cancer patient cohort (1306) of our diagnostic center, where the two tests have been run parallel in 703 cases.

Method: IHC of the MMR proteins was performed on FFPE blocks by using ready-to-use mouse monoclonal antibodies of Ventana, anti- MLH1, anti-MSH2, anti-PMS2 and rabbit monoclonal anti-MSH6 . The immunoreaction was developed by the DAB Ultraview kit in the BenchmarkUltra automatic stainer (Ventana). For MSI-PCR, the DNA extraction was the first step. DNA was then amplified by PCR for five mononucleotide microsatellite markers (BAT-25, BAT-26, MONO-27, NR-21, NR-24) and two pentanucleotide markers (Penta C and Penta D as internal technical controls) using Promega MSI Analysis System Version 1.2, followed by fragment analysis using ABI 3730 Genetic Analyzer.

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 very low (41.1%), while it diverse in classic IHC resulted relatively low positive (91.6%) and negative (80.5%) predicting values. The correlation tests indicated a modestly low rate between the two methods (κ:~0.5–0.3), not reaching the expected cut-off 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, non-classic, unusual) as possible contributors, since sensitivity differed in each type (62.7%, 37.2%, 5.1%).

Conclusion. Although our cohort did not include samples with identified technical errors, our
data strongly support previous reports that unidentified preanalytical factors might have the
major influence on the poor performance of the MSI PCR and MMR IHC. Furthermore, the
case is open whether the two test types are equally powerful predictive markers of
immunotherapies.

University

Semmelweis University

Supervisor

Prof. Dr. Tímár József

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8074

Start

10:45

End

10:55