Lynch Syndrome in Colorectal Cancer: Recommended Evaluation Approach

Clinical Scenario

In patients with colorectal cancer, Lynch syndrome — a hereditary condition affecting DNA mismatch repair — must be considered. Because the condition is frequently undetected without systematic testing, current guidance supports a universal screening approach at the time of colorectal cancer diagnosis.

Why Colorectal Cancer Matters Here

All patients with colorectal cancer are candidates for Lynch syndrome evaluation, regardless of age or family history. Tumor testing — using immunohistochemistry (IHC) or microsatellite instability (MSI) analysis — is the recommended first step to identify cases that warrant further workup, rather than foregoing testing entirely.

Evaluation Pathway (Overview)

When initial tumor testing raises a specific pattern of abnormality, a second-stage tumor test is recommended before proceeding to germline genetic testing. This additional molecular step helps distinguish hereditary Lynch syndrome from other causes.

The complete testing algorithm, decision criteria, and clinical sequence are detailed in the full protocol below.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1053/j.gastro.2015.07.036

The AGA recommends testing the tumors of all patients with colorectal cancer with either immunohistochemistry (IHC) or for microsatellite instability (MSI) to identify potential cases of Lynch syndrome versus doing no testing for Lynch syndrome.

The AGA suggests that in patients with colorectal cancer with IHC absent for MLH1, second-stage tumor testing for a BRAF mutation or for hypermethylation of the MLH1 promoter should be performed rather than proceeding directly to germline genetic testing.

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