Abstract
BackgroundLynch syndrome is the most common hereditary colorectal cancer syndrome, and adenoma is one of the important premalignant lesions to colorectal cancer in Lynch syndrome. The first objective of this study was to calculate the detection rate of Lynch syndrome in colorectal polyps by using mismatch repair immunohistochemistry as the initial screening strategy. The second objective of this study was to optimize screening strategies for adenoma associated with Lynch syndrome by integrating polyp and/or patient characteristics such as polyp size, location, dysplasia, age of onset and/or family history of cancer.MethodsFrom June 2014 to May 2016, immunohistochemistry was performed for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) using endoscopically resected specimens obtained from newly diagnosed colorectal adenomas. Gene analysis was performed in patients with missing expression of mismatched repair protein.ResultsFive hundred and ten patients underwent colorectal polyp resection, with a total of 718 polyps. Five hundred and eight resected adenomas underwent mismatch repair protein immunohistochemical testing. Loss of mismatch repair protein expression was observed in six adenomas, accounting for 1.18% of all adenomas. Five patients then underwent genetic tests to identify two pathogenic mutations from different individuals, while another patient was suspected to have a pathogenic mutation. Three patients were younger than 50 years old. Two patients had advanced histology (high-grade dysplasia and malignant components) and one patient had a family history of cancer.ConclusionImmunohistochemical detection of colorectal polyp mismatch repair protein as Lynch syndrome screening efficiency is low. Effective screening strategies may be improved by optimizing patient/polyp selection, such as focusing on young adenoma patients with a family history of cancer, or patients who present with high-risk features (large size, villous, high-grade dysplasia and malignant components).
Highlights
Lynch syndrome (LS) is the most common disease that causes hereditary colorectal cancer syndrome, accounting for approximately 2–5% of all colorectal cancers [1], caused by autosomal dominant inheritance of a germline mutation in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6,and PMS2) or EPCAM gene deletion
Immunohistochemistry (IHC) examining loss of expression (LOE) of one or more MMR proteins can be performed on adenomas as a screening test for LS, and subsequent
Some studies suggest the rate of LOE in MMR proteins or microsatellite instability (MSI) in sporadic adenomatous polyps is low (< 2%) [6,7,8]
Summary
Lynch syndrome (LS) is the most common disease that causes hereditary colorectal cancer syndrome, accounting for approximately 2–5% of all colorectal cancers [1], caused by autosomal dominant inheritance of a germline mutation in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6,and PMS2) or EPCAM gene deletion. Some studies suggest the rate of LOE in MMR proteins or microsatellite instability (MSI) in sporadic adenomatous polyps is low (< 2%) [6,7,8]. Lynch syndrome is the most common hereditary colorectal cancer syndrome, and adenoma is one of the important premalignant lesions to colorectal cancer in Lynch syndrome. The first objective of this study was to calculate the detection rate of Lynch syndrome in colorectal polyps by using mismatch repair immunohistochemistry as the initial screening strategy. The second objective of this study was to optimize screening strategies for adenoma associated with Lynch syndrome by integrating polyp and/or patient characteristics such as polyp size, location, dysplasia, age of onset and/or family history of cancer
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