Which molecular pathway, characterised by widespread microsatellite instability (MSI-H) due to deficient mismatch repair (dMMR), confers a paradoxically better prognosis in stage II colorectal cancer but predicts resistance to standard 5-FU-based adjuvant chemotherapy?

• A Microsatellite instability (MSI-H/dMMR) pathway ✓
• B CpG island methylator phenotype (CIMP) with BRAF V600E mutation
• C Chromosomal instability (CIN) pathway with APC mutation
• D RAS pathway activation with KRAS exon 2 mutation

Explanation

The MSI-H/dMMR pathway (affecting ~15% of colorectal cancers) is associated with a better overall prognosis in localised (stage II) disease due to enhanced immune surveillance. Paradoxically, these tumours are resistant to 5-FU monotherapy, so adjuvant chemotherapy is not recommended for stage II dMMR/MSI-H patients unless they have high-risk features. Importantly, dMMR/MSI-H tumours show remarkable responses to immune checkpoint inhibitors (pembrolizumab). BRAF V600E often co-occurs with MSI-H/CIMP but confers a poor prognosis in metastatic disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.