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

摘要

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 pre‐malignant polyps remains controversial. Aim To determine the effectiveness of mismatch repair immunohistochemistry performed on pre‐malignant 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 were 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 three individuals with concordant germline variants in two patients (one PMS2 variant of unknown significance and one 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.