Performance of immunohistochemical and molecular methods in detecting microsatellite instability in gastric cancer: a multicenter study

Diogo Sousa Marques, Irene Gullo, Luís Mascarenhas-Lemos, João Ricardo Silva, Catarina Neto do Nascimento, Patricia Pontes, Lidia Pinho, Luis Cirnes, Xiaogang Wen, Marilia Cravo, Fátima Carneiro

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Introduction: Introduction: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla MSI assay has not been validated for GC but may prove to be a valid alternative.Methods: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0.Results: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only three cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla.Conclusion: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.
Original languageEnglish
Pages (from-to)389-399
Number of pages11
JournalPathobiology
Volume90
Issue number6
DOIs
Publication statusPublished - 1 Dec 2023

Keywords

  • Diagnostic accuracy
  • Gastric cancer
  • Idylla
  • Immunohistochemistry
  • Microsatellite instability
  • Mismatch-repair proteins
  • Multiplex polymerase chain reaction

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