Diagnostic and Prognostic Significance of Microsatellite Instability in Endoscopic Biopsies from Patients with Gastric Adenocarcinoma: A Review

Abstract

Microsatellite instability decides treatment in gastric adenocarcinoma well before a stomach is removed. Chemotherapy is chosen, or withheld, on thestrength of a few millimetres of tissue taken at endoscopy, which makes the reliability of that small sample a clinical  question rather than a laboratory one. Objectives: To review what published evidence shows about the accuracy of MSI and mismatch repair testing on endoscopic biopsies against the resection specimen, the prevalence of MSI-high disease across clinical settings, and the prognostic and predictive weight the result carries once obtained. Material and Methods: Narrative review of matched-sample diagnostic studies, randomised trial analyses and prospective cohorts indexed in PubMed and the major oncology journals. Studies were eligible if they reported paired biopsy and surgical MSI or MMR results, MSI-high prevalence in a defined gastric or gastroesophageal population, or outcomes stratified by MSI status. No new patient data were generated. All frequencies, hazard ratios and response rates quoted are those published by the original investigators. Results: In paired samples, endoscopic biopsy performed well against the resection specimen, with concordance of 96.2 per cent by PCR and 97.8 per cent by immunohistochemistry, and specificity of 98 per cent for both. Sensitivity was lower, at 85 and 86 per cent. Biopsy material was more often uninformative by IHC than by PCR. In a cohort restricted to MSI-high cases, discrepancy between biopsy and resection reached 19.7 per cent, consistent
with clonal heterogeneity of mismatch repair loss. Prevalence falls as disease advances, from around 12 per cent in resectable series to 4.0 per cent in third-line trial populations. In the MAGIC trial, MSI-high or dMMR status was associated with better survival after surgery alone (HR 0.42) and worse survival when chemotherapy was added (HR 2.18, 95% CI 1.08-4.42), with median overall survival of 9.6 against 19.5 months in the chemotherapy arm. Response to pembrolizumab in MSI-high advanced disease reached 57.1 per cent in third line and above. Conclusion: Endoscopic biopsy is an adequate substrate for MSI and MMR testing, and the published concordance figures support testing at diagnosis rather than waiting for a resection specimen. The qualification is that errors are asymmetric: a positive biopsy result is close to definitive, while a negative one carries a real false-negative rate driven by sampling. Because a positive result may argue against chemotherapy and in favour of immunotherapy, that asymmetry has direct consequences for treatment.
Abbreviations: MSI – Microsatellite Instability, MSI-H – Microsatellite Instability-High, MSS – Microsatellite Stable, MMR – Mismatch Repair, dMMR – Deficient Mismatch Repair, pMMR – Proficient Mismatch Repair, IHC – Immunohistochemistry, PCR – Polymerase Chain Reaction, GEJ – Gastroesophageal Junction, ORR – Objective Response Rate, OS – Overall Survival, HR – Hazard Ratio.