The Utility of Immunohistochemistry for Mismatch Repair Proteins on Colorectal Polyps in the Familial Cancer Clinic.

Dow E1, Buchanan DD1,2,3,4, Winship IM1,5.

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Abstract

BACKGROUND:

Immunohistochemistry for loss of expression of one or more of the mismatch repair proteins is performed on colorectal cancer tissue as a screening test for Lynch syndrome; however, its role in premalignant polyps remains controversial.

AIM:

To determine the effectiveness of mismatch repair immunohistochemistry performed on premalignant colorectal polyps in identifying Lynch syndrome, focusing on clinical utility and value.

METHODS:

A retrospective audit was conducted of mismatch repair immunohistochemistry performed on non-malignant polyps in patients who attended the Family Cancer Clinic at the Royal Melbourne Hospital. Two hundred and six patient records over a 10 year period (2006-2016) were reviewed. Personal and family history data was collected, including genetic testing results.

RESULTS:

Of the 57 patients who underwent polyp testing, the family histories comprised Amsterdam II Criteria (12.3%), Lynch syndrome-associated malignancies (42.1%), Lynch syndrome-associated malignancies and polyps (35.1%), and polyps only (8.8%); 10.5% of patients had no significant family history. Normal expression of the mismatch repair proteins was observed in 94.7% of patients; loss of expression was observed in 3 individuals with concordant germline variants in 2 patients (1 PMS2 variant of unknown significance and 1 MSH6 mutation). Additional genetic testing in 21 patients with normal immunohistochemistry did not identify any additional Lynch syndrome cases.

CONCLUSION:

The clinical utility of mismatch repair immunohistochemistry on polyp tissue was low. No additional cases of Lynch syndrome were identified, and a large proportion of patients proceeded to germline testing despite normal polyp immunohistochemistry. We suggest there is no value in this approach.