Relevance, pathogenesis, and testing algorithm for mismatch repair-defective colorectal carcinomas: a report of the association for molecular pathology.

摘要: Loss-of-function defects in DNA mismatch repair (MMR), which manifest as high levels of microsatellite instability (MSI), occur approximately 15% all colorectal carcinomas (CRCs). This molecular subset CRC characterizes patients with better stage-specific prognoses who experience no benefit from 5-fluorouracil chemotherapy. Most MMR-deficient (dMMR) CRCs are sporadic, but to 20% due inherited predisposition (Lynch syndrome). High penetrance germline MMR gene mutation carriers emphasizes the importance accurate diagnosis Lynch syndrome carriers. Family-based (Amsterdam), patient/family-based (Bethesda), morphology-based, microsatellite-based, and IHC-based screening criteria do not individually detect These limitations support use multiple concurrent tests newly diagnosed CRC. approach is resource intensive would increase detection de novo mutations guide family screening. Although prognosis prediction response similar both sporadic dMMR subgroups, these subgroups differ significantly regard implications for members. We recommend that new should be classified into MMR-proficient, dMMR, or subgroups. The MSI testing, protein IHC, BRAF c.1799T>A analysis almost CRCs, classify 94% secondary testing remainder.