A single center study of colorectal cancer screening for Lynch syndrome

Objective To determine the ratio of deficient mismatch repair (dMMR) proteins and Lynch syndrome among patients undergoing colorectal cancer resection. Methods From June 2014 to May 2016, immunohistochemistry for mismatch repair proteins including mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and PMS1 homolog 2 (PMS2) were carried out on 207 surgically resected specimens. Samples with lost expression of MMR proteins underwent genetic testing. Results Loss of expression of MMR proteins were found among 21 patients and accounted for 10.14% of the colorectal cancers. dMMR was more common in patients ≤50 years old, or with proximal tumor at splenic flexure and mucinous adenocarcinoma. Ten patients underwent genetic testing, with three pathogenic mutations (MSH6 c. 3013C>T, MLH1 c. 199G>A and a novel MSH6c.584delT) and four ambiguous mutations identified. At least 1.4% of the colorectal cancers were diagnosed as Lynch syndrome. Conclusion Routine screening for Lynch syndrome among patients with colorectal cancer with MMR protein immunohistochemistry as preliminary screening method and MMR gene sequencing as diagnostic method is effective and feasible. It can reduce missed diagnosis of Lynch syndrome and bring lifelong benefit to patients and their families. Key words: Lynch syndrome; Colorectal cancer; Screening; Immunohistochemistry; Genetic testing