Microsatellite instability (MSI-H) in colorectal carcinoma has which of the following clinical-pathological implications for treatment decision-making?

• A Stage II MSI-H tumors benefit from adjuvant 5-fluorouracil-based chemotherapy
• B MSI-H status predicts resistance to immune checkpoint inhibitors
• C MSI-H is associated with left-sided, well-differentiated tumors
• D Stage II MSI-H tumors have a better prognosis and do NOT benefit from adjuvant 5-FU chemotherapy ✓

Explanation

MSI-H (high microsatellite instability, also termed dMMR — deficient mismatch repair) colorectal cancers paradoxically have a better prognosis in stage II disease compared to MSS tumors (reflecting intact immune surveillance). However, multiple studies (including QUASAR and MOSAIC subgroup analyses) have consistently shown that stage II MSI-H tumors do NOT benefit from adjuvant 5-fluorouracil-based chemotherapy — the hazard ratio favors no treatment or is neutral. This is because MSI-H tumors have high frameshift-derived neoantigens making them highly immunogenic and respond well to checkpoint inhibitors (pembrolizumab) but are intrinsically resistant to 5-FU. MSI-H tumors tend to be right-sided, poorly differentiated, and mucinous.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

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Written and medically reviewed by the StethoPrep medical team.