Characterization of discordance between mismatch repair deficiency and microsatellite instability testing may prevent inappropriate treatment with immunotherapy

• DOI: 10.1002/path.6279
• Publication Date: 2024-05-15T09:54:33Z
• Authors: Birgit S Geurts; Laurien J Zeverijn; Jade M van Berge ...; Hanneke van der W...; Louisa R Hoes; Gijs F de Wit; Ilse AC Spiekman; Thomas W Battaglia; Daphne M van Beek; Paul Roepman; Anne ML Jansen; Wendy WJ de Leng; Annegien Broeks; Mariette Labots; Carla ML van Herpen; Hans Gelderblom; Henk MW Verheul; Petur Snaebjornsson; Emile E Voest
• Keywords: Microsatellite Instability; Immune checkpoint

Abstract In the Drug Rediscovery Protocol (DRUP), patients with cancer are treated based on their tumor molecular profile approved targeted and immunotherapies outside labeled indication. Importantly, undergo a biopsy for whole‐genome sequencing (WGS) which allows WGS‐based evaluation of routine diagnostics. Notably, we observed that not all biopsies dMMR/MSI‐positive tumors as determined by diagnostics were classified microsatellite‐unstable subsequent WGS. Therefore, aimed to evaluate discordance rate between dMMR/MSI WGS further characterize discordant cases. We assessed enrolled in DRUP identified diagnostics, who immune checkpoint blockade (ICB) whom data available. Patient characteristics, study treatment outcomes, material from care retrieved patient medical records via Palga (the Dutch Pathology Registry), compared results. Initially, was 13 (13/121; 11%). The majority these did benefit ICB (11/13; 85%). After characterization, found six (5%) caused dMMR harbor an MSI phenotype (5%), false due presence multiple primary ( n = 3, 2%) misdiagnosis status immunohistochemistry 2%). one (1%), exact underlying cause could be identified. Thus, this group limited those initially diagnosed current true assay‐based 5%. To prevent inappropriate treatment, clinicians pathologists should aware risk limitations different tests. © 2024 Pathological Society Great Britain Ireland.