Consistency and Heterogeneity of Microsatellite Instability (MSI) Status in Paired Biopsy and Surgical Specimens of Colorectal Cancer: A Necessity for MSI Reassessment After Treatment?

Abstract

Purpose: Microsatellite instability (MSI) is a vital biomarker for cancer immunotherapy and prognosis, necessitating precise detection. However, data on MSI status changes following neoadjuvant therapy (NT) and standardized testing in biopsy samples are limited. The study aimed to investigate the concordance of MSI status between paired biopsy and surgical samples, as well as the impact of NT on MSI status using a novel MSI next-generation sequencing (MSI-NGS) detection panel.

Methods: Involving 137 patients with colorectal cancer (CRC), 116 with matched biopsies and surgical samples were analyzed. A custom MSI-NGS panel was used and its performance was compared with MSI polymerase chain reaction (MSI-PCR), which served as the gold standard.

Results: The MSI-NGS panel showed 97% accuracy, with 112 patients exhibiting consistent MSI status between samples. In both surgical and biopsy samples, 3% of patients had MSI-high by MSI-NGS but microsatellite stable by MSI-PCR, whereas 1% had the opposite results. Both the surgical and biopsy samples demonstrated an overall discrepancy of 4% for both methodologies. Neoadjuvant chemotherapy in eight patients did not alter MSI status. Compared with F1CDx, MSK-IMPACT, and a 556-gene panel including146 MSI loci, the NGS panel exhibits higher accuracy, as well as excellent specificity.

Conclusion: There is a high consistency in the detection of MSI status between surgical and biopsy samples. Moreover, the study confirms the reliability of the MSI-NGS panel for MSI detection in limited biopsy specimens.