Prevalence and clinicopathologic/molecular characteristics of mismatch repair-deficient colorectal cancer in the under-50-year-old Japanese population

Purpose To clarify the prevalence and clinicopathologic/molecular characteristics of mismatch repair (MMR)-deficient colorectal cancer in the young Japanese population. Methods Immunohistochemical analyses for MMR proteins (MLH1, MSH2, MSH6, and PMS2) were performed in formalin-fixed paraffin-embedded sections prepared from the resected CRC specimens of 119 consecutive patients aged < 50 years old, who underwent resection of the primary tumor at our institution between 1996 and 2015. Analyses for somatic BRAF V600E mutation, somatic hypermethylation of the MLH1 promoter, and germline MMR gene mutations were undertaken where indicated. Results MMR protein loss was found in 10 patients (8.4%), 7 (5.9%) of whom were subsequently identified to have Lynch syndrome (LS). The remaining 3 patients were categorized as having sporadic MMR-deficient CRC (n = 2) or "possible LS (n = 1)". In multivariate logistic regression analysis, the presence of tumor-infiltrating lymphocytes (P < 0.01), right-sided location of the tumor (P = 0.01), and a history of LS-associated tumors in the first-degree relatives (P < 0.01) were identified as independent factors predictive of MMR-deficient CRC. Conclusion These results are of value in the clinical management of patients with the early onset CRC under circumstances where universal tumor screening approaches for LS are still not available, like in Japan.