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Rawia Mohamed: Data on MMR and MSI testing in paired biopsy and surgical specimens from resectable GC/GEJC

cancerhealth.com

Feb 3, 2025, 05:44

Rawia Mohamed: Data on MMR and MSI testing in paired biopsy and surgical specimens from resectable GC/GEJC

Rawia Mohamed, Head of the Anatomical Pathology Department at Burjeel Medical City and an Associate Professor at Khalifa University, shared a post on LinkedIn:

“Concordance of MSI and MMR in Paired Biopsies and Surgical Specimens of Resectable Gastric Cancer (GC) and Gastroesophageal Junction Cancer (GEJC). This slide presents data on mismatch repair (MMR) and microsatellite instability (MSI) testing in paired biopsy and surgical specimens from resectable gastric and gastroesophageal junction cancers (GC/GEJC). The key focus is on discordance rates, which impact treatment decisions, particularly for immunotherapy selection.

Key Findings in this study:

A. Discordance in MSI/MMR Testing
66 paired biopsy and surgical specimens were analyzed.
13 out of 66 cases (19.7%) showed discordance between MMR/IHC and MSI/PCR results.
Majority (80.3%) showed concordant results, meaning biopsy and resection results matched.

B. Discordant Cases in this study:

4 cases had MMR IHC misinterpretation.
4 cases had sample quality/quantity issues, affecting test accuracy.
3 cases involved tissue unavailability for revision.
1 case had a pathological misdiagnosis.
1 case showed discordance between IHC and PCR testing.
2. Clinical Implications

A. Importance of Multi-Site Testing.

MMR/MSI testing may differ between biopsies and resection specimens due to tumor heterogeneity. Multi-region sampling is crucial, especially for MSI-H tumors, which are eligible for immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab).

B. Potential Causes of Discordance.

Tumor Heterogeneity: MSI/MMR status may differ across tumor regions.
Technical Errors: Differences in fixation, staining, or PCR conditions can impact results.
Pathologist Interpretation Variability: MMR IHC scoring can be subjective, leading to misinterpretation.”

Take home message:

MSI/MMR testing is not always concordant between biopsy and resection specimens (19.7% discordance in this study). Tumor heterogeneity, technical issues, and pathologist interpretation errors contribute to discordance. Multi-region sampling and confirmatory testing (e.g., MSI-PCR) can improve diagnostic accuracy. Discordance must be carefully evaluated to ensure proper treatment selection, especially for immunotherapy candidates. ASCO/CAP guidelines recommend confirmatory MSI-PCR testing if MMR IHC results are equivocal. Re-biopsy or testing additional regions may be necessary if initial results are discordant.”