Molecular Screening for Lynch Syndrome in Young Patients With Colorectal Adenomas

Utility of immunohistochemistry for mismatch repair proteins on colorectal polyps in the familial cancer clinic

“…Given the low clinical utility and value of polyp MMR IHC, which has been previously demonstrated in the literature 5,9,11,12 and confirmed in this study, the clinical practice of ordering such testing should be examined. In our cohort, MMR IHC testing was requested by multiple FCCassociated clinicians, including geneticists, gastroenterologists and medical oncologists.…”

“…4 Similarly, a significant association between high grade dysplasia and high levels of MSI has been demonstrated. 5 While adenoma MSI testing in a young (<40 years old) Portuguese cohort found that MSI correlated with the identification of a germline LS mutation in 85.7% cases, though all cases had Amsterdam Criteria-positive family histories. 4 However, these studies were all carried out in LS patients and provide little insight on the use of polyp MMR IHC in screening for LS.…”

“…9 A recent study demonstrated MMR IHC performed on adenomas from young patients (age <50 years) not known to have LS, nor having a suggestive family history, was abnormal in only 0.4% of cases. 5 While adenoma MSI testing in a young (<40 years old) Portuguese cohort found that MSI correlated with the identification of a germline LS mutation in 85.7% cases, though all cases had Amsterdam Criteria-positive family histories. 10 This suggests the rate of abnormal MMR IHC or MSI in sporadic adenomatous polyps is low (<2%), 9,11,12 and that screening of polyps may be effective in identifying new cases of LS.…”

“…3 This raises the possibility of performing MMR IHC on pre-malignant polyps as a screening tool for LS, particularly as an early detection strategy in young patients. 5 Previous studies of polyp MMR IHC have yielded mixed results. 4 However, identification of LS families is vital for cancer risk management through surveillance, and/or risk-reducing strategies.…”

“…4 However, identification of LS families is vital for cancer risk management through surveillance, and/or risk-reducing strategies. 5 Previous studies of polyp MMR IHC have yielded mixed results. Adenomas from LS patients have rates of abnormal MMR IHC from 50% to 80%, 4,6,7 and rates of MSI from 57% to 93%.…”